To compare the efficacy of an intracanalicular dexamethasone intracanalicular insert (DII) to a topical prednisolone acetate 1% taper for preventing breakthrough inflammation (iritis or cystoid macular edema) during the first post-operative month (POM1) after cataract surgery DESIGN: Retrospective, non-randomized comparative interventional study METHODS: Patients received either DII or topical prednisolone acetate 1% eyedrops (control) during POM1. Exclusion criteria included history of iritis, glaucoma, intraoperative posterior capsular rupture or vitreous prolapse, immediate postoperative anterior chamber inflammation requiring treatment, or less than 1 month follow up post-operatively. Outcomes included development of breakthrough inflammation after >3 days postoperatively necessitating additional anti-inflammatory drops, cystoid macular edema, and increased intraocular pressure at POM1. 266 eyes of 174 patients were included in the DII group, and 258 eyes of 167 patients in the control group. Demographics, comorbidities, and baseline IOP were comparable between groups. The breakthrough inflammation rate was significantly higher in the DII group compared to control (9.0% vs 3.1%; p < .01); cystoid macular edema rates were similar between groups (4.9% vs 4.3%; p = .75). There were no cases of increased IOP >10mmHg at POM1 compared to baseline in either group. After cataract surgery, DII demonstrated a higher rate of breakthrough inflammation than a standard topical steroid regimen with no significant differences in CME rate or IOP increase; however, overall, the rate of postoperative complications was low. DII can be a safe and effective alternative to topical corticosteroid therapy after cataract surgery.