<h3>Objective:</h3> The goal was to compare the biodistribution, efficacy and side-effects of deflazacort, prednisolone and vamorolone in the wild-type adult mice and the <i>mdx-B10</i> DMD mouse model. <h3>Background:</h3> Corticosteroids are the standard of care for patients with Duchenne muscular dystrophy (DMD). In this report, we present the first direct comparison of three corticosteroids: deflazacort, prednisolone and vamorolone in mice. <h3>Design/Methods:</h3> The pharmacokinetics and biodistribution of deflazacort, prednisolone and vamorolone were evaluated in wild-type adult mice after oral administration. Efficacy was evaluated in adult <i>mdx</i>-B10 DMD mice by measuring grip strength. Side-effects were evaluated by monitoring changes in behavior, bone density, endogenous corticosteroid levels, and blood glucose levels. Changes in gene expression in the brain, liver, and muscle were evaluated using RNA sequencing. <h3>Results:</h3> These compounds differed in their biodistribution in the mouse CNS, with deflazacort showing a lower brain:plasma ratio (0.05) than vamorolone (0.55). All three corticosteroids demonstrated efficacy in <i>mdx</i> mice and side-effects at doses associated with efficacy. After 14 days of treatment, prednisolone and vamorolone extensively altered gene expression in the brains of <i>mdx</i> mice, compared with deflazacort. All three corticosteroids induced extensive changes in gene expression in the muscle and the liver. After 28 days, <i>mdx</i> mice treated with deflazacort showed a greater improvement in grip strength than those treated with prednisolone or vamorolone. Vamorolone and prednisolone induced greater depression than deflazacort (1.6-fold longer in time spent immobile for vamorolone- and prednisolone-treated mice, with no increase in time spent immobile for deflazacort-treated mice). <h3>Conclusions:</h3> This is the first direct comparison of the dose response of deflazacort, prednisolone and vamorolone in wild-type adult mice and a mouse model of DMD. Deflazacort was the most effective in increasing muscle strength, as measured by the grip test. Furthermore, of the three corticosteroids, deflazacort resulted in the fewest behavioral side-effects. <b>Disclosure:</b> Dr. Liu has nothing to disclose. Mr. Lipari has received personal compensation for serving as an employee of PTC Terapeutics. Mrs. Mollin has received personal compensation for serving as an employee of PTC Therapeutics. Mrs. Mollin has stock in PTC THERAPEUTICS. Mr. Jung has received personal compensation for serving as an employee of PTC Therapeutics. Mr. Jung has stock in AbbVie. Mr. Jung has stock in Agilon Health. Mr. Jung has stock in AmeriSourceBergen. Mr. Jung has stock in Abbott Laboratories. Mr. Jung has stock in Aflac. Mr. Jung has stock in Amgen. Mr. Jung has stock in Axa SA. Mr. Jung has stock in BASF. Mr. Jung has stock in Becton, Dickinson and Co. Mr. Jung has stock in BeiGene. Mr. Jung has stock in Boston Scientific. Mr. Jung has stock in Cardinal Health. Mr. Jung has stock in Cigna. Mr. Jung has stock in CNO Financial Group. Mr. Jung has stock in DexCom. Mr. Jung has stock in Icon plc. Mr. Jung has stock in Medtronic plc. Mr. Jung has stock in Elevance Health. Mr. Jung has stock in EXACT Sciences. Mr. Jung has stock in CVS Health. Mr. Jung has stock in Centene. Mr. Jung has stock in Certara. Mr. Jung has stock in Colgate-Palmolive. Mr. Jung has stock in Danaher. Mr. Jung has stock in DuPont de Nemours. Mr. Jung has stock in Edwards Lifesciences. Mr. Jung has stock in Elekta. Mr. Jung has stock in General Electric. Mr. Jung has stock in Genmab A/S. Mr. Jung has stock in Gilead Sciences. Mr. Jung has stock in HCA Healthcare. Mr. Jung has stock in Hologic. Mr. Jung has stock in Illumina. Mr. Jung has stock in Incyte. Mr. Jung has stock in Intuitive Surgical. Mr. Jung has stock in Iqvia Holdings. Mr. Jung has stock in Kimberly Clark. Mr. Jung has stock in Lifestance Health Group. Mr. Jung has stock in McKesson. Mr. Jung has stock in MetLife. Mr. Jung has stock in Moderna. Mr. Jung has stock in Omega Healthcare Investors. Mr. Jung has stock in Omron. Mr. Jung has stock in Proctor & Gamble. Mr. Jung has stock in Reckitt Benckiser Group plc. Mr. Jung has stock in Regeneron Pharmaceuticals. Mr. Jung has stock in Shockwave Medical. Mr. Jung has stock in Siemens AG. Mr. Jung has stock in Siemens Healthineers ADR. Mr. Jung has stock in Straumann Holding ADR. Mr. Jung has stock in Stryker. Mr. Jung has stock in Terumo. Mr. Jung has stock in Thermo Fisher Scientific. Mr. Jung has stock in 3M. Mr. Jung has stock in Unicharm. Mr. Jung has stock in UnitedHealth Group. Mr. Jung has stock in Vertex Pharmaceuticals. Mr. Jung has stock in Walmart. Mr. Jung has stock in Alnylam Pharmaceuticals. Dr. Teplova has nothing to disclose. Ms. Ma has nothing to disclose. Dr. LI has received personal compensation for serving as an employee of PTC Therapeutics. Dr. LI has stock in PTC Therapeutics. Ms. Ying has received personal compensation for serving as an employee of PTC Therapeutics. Mrs. Yeh has nothing to disclose. Dr. Narasimhan has received personal compensation for serving as an employee of PTC Therapeutics Inc. Dr. Narasimhan has stock in PTC Therapeutics Inc. Dr. Narasimhan has received intellectual property interests from a discovery or technology relating to health care. Panayiota Trifillis has received personal compensation for serving as an employee of PTC Therapeutics. Panayiota Trifillis has received stock or an ownership interest from PTC Therapeutics, Inc.. Panayiota Trifillis has received intellectual property interests from a discovery or technology relating to health care. Efthimia Leonardi has received personal compensation for serving as an employee of PTC Therapeutics, Inc. Efthimia Leonardi has stock in {TC Therapeutics Inc. Ms. Welch has received personal compensation for serving as an employee of PTC Therapeutics. Ms. Welch has stock in PTC Therapeutics. Dr. Voronin has received personal compensation for serving as an employee of PTC Therapeutics. Dr. Voronin has stock in PTC Therapeutics. Dr. Dong has nothing to disclose. Nick Mastrandrea has received personal compensation for serving as an employee of PTC Therapeutics. Nick Mastrandrea has stock in PTC Therapeutics. Dr. Blaize has stock in PTC Therapeutics Inc. Dr. Weetall has received personal compensation for serving as an employee of PTC Therapeutics.