Background: The objective of this study was to examine the feasibility, safety, and efficacy of 10 Hz repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder in adolescents. Methods: Adolescent subjects with treatment resistant depression (n=103) aged 12-21 were enrolled in multicenter, randomized, sham-controlled trial of rTMS. Inclusion criteria included a score of 2 or more on item 1 of the Hamilton Depression Rating Scale (HAMD-24) a total score of 20 or greater. Treatment resistance was defined as an ATR level of 1-4 in a current, discrete episode of depression. Subjects were randomized to either active NeuroStar TMS Therapy (n=48) or sham rTMS (n=55) for 30 daily treatments over 6 weeks as monotherapy. The primary outcome measure was the HAMD-24. Results: There were no baseline differences in demographics among the two arms. After 6 weeks of blinded treatment the LS mean (SE) HAMD-24 changes were 11.1 (2.03) in the active group and 10.6 (2.00) in the sham group with no statistically significant difference (p= 0.8, 95% CI -0.5 [-4.2, 3.3]). The response rate was 41.7% in the active group and 36.4% in the sham group (p= 0.6). The tolerability and safety findings were similar to existing adult data. Conclusions: Based on the largest study of adolescents to date, Left prefrontal 10 Hz rTMS monotherapy appears to be feasible, tolerable, and safe in adolescents with treatment resistant depression. Future studies should focus on study designs to reduce placebo response rates, larger sample size, and dose finding approaches for adolescents with depression. Funding: The study was funded by Neuronetics Disclosures: Dr. Croarkin has received research grant support from the National Institute of Mental Health, Brain and Behavior Research Foundation, and Pfizer, Inc. He has received equipment support from Neuronetics, Inc. and received supplies and genotyping services from Assurex Health, Inc. for investigator-initiated studies. He is the primary investigator for a multicenter study funded by Neuronetics, Inc. and a site primary investigator for a study funded by NeoSync, Inc. Dr. Croarkin has served as a paid consultant for Procter & Gamble Company and Myriad Neuroscience. Dr. Elmaadawi receives research support from Duke University and University of North Western. He receives research fund from Neurocrine, Inc and Neuronetics, Inc. He is also a speaker for Neuronetics, Inc. Dr. Aaronson has received research support from Compass Pathways and Neuronetics. He serves as a consultant to LivaNova, Neuronetics, Janssen, Genomind, and Sage Therapeutics. He is also on the speaker boards for Janssen and Sunovion. Dr. Schrodt has had consultation fees from Neuronetics. Dr. Holbert has received equipment support from Neuronetics, Inc. Ms. Verdoliva is an employee of NAMSA. NAMSA provides testing, consulting, and contract medical research services to the medical device industry. Ms. Heart is an employee of Neuronetics. Dr. Demitrack is a consultant to Neuronetics, Inc. and a full-time employee of Trevena, Inc. Dr. Strawn has received research support from Allergan, Neuronetics, Otsuka, the National Institutes of Health (National Institute of Mental Health, National Institute of Child Health and Development and National Institute of Environmental Health Sciences) and the Yung Family Foundation. He receives royalties from Springer Publishing and received honoraria from CMEology and Neuroscience Educational Institute. He receives royalties from UpToDate. Finally, he received material support from and provided consultation to Myriad Genetics.