Purpose: To evaluate the real-life efficacy and safety of the intravitreal dexamethasone implant (DEX-I) in uveitis. Methods: This retrospective observational multicentric study included 152 eyes treated exclusively by 358 DEX-I. The main outcome measures included change in best-corrected visual acuity (BCVA), central macular thickness (CMT) and vitreous haze score. Results: Patients were treated with DEX-I for macular edema (ME) (51.3%), vitritis with ME (40.1%), vitritis (5.3%) and other causes (3.3%). The mean duration of follow up was 19.0 months. The mean gain in BCVA during follow-up was +12.1 letters. An improvement in BCVA ≥ 5, 10 and 15 letters was found in 64.5%, 50.7% and 35.5% of cases respectively. 59.7% eyes with ME at baseline were found to be anatomical responders. Vitritis resolution (vitreous haze = 0+) was obtained in 81.4% of cases. Ocular hypertension (IOP ≥25 mmHg and/or gain ≥10 mmHg from baseline) occurred in 28.3% of patients. No filtering surgery/laser therapy was required. A total of 40.2% of phakic subjects underwent cataract surgery on average 11.2 months after the first injection. Conclusion: This study confirms the efficacy and safety of the DEX-I in non-infectious uveitis. Cataract and ocular hypertension were not uncommon but easily manageable.