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Purpose: Cytomegalovirus is an increasingly recognized cause of anterior uveitis. We present clinical features of cytomegalovirus anterior uveitis (CMVAU) and outcomes of oral valganciclovir treatment at a tertiary referral center in North America., Methods: This is a retrospective case series review (2002-2014) of immunocompetent patients with CMVAU treated with valganciclovir 900 mg BID and subsequent maintenance dosing of ≤450 mg BID. Most patients were prescribed topical corticosteroids concurrently. Diagnostic evaluations and clinical features at baseline and follow-up were reviewed. Resolution time, maintenance of quiescence, and adverse events were assessed., Results: Eighteen eyes of 16 patients were included. The mean age of diagnosis was 41 years. At diagnosis, mean best-corrected visual acuity was 0.30 LogMAR and mean intraocular pressure (IOP) was 18.4 mm Hg; 14 eyes (78%) had an active anterior chamber (AC) cell, 8 (44%) had circinate keratic precipitates, and 6 (33%) had iris atrophy. The mean follow-up duration was 48 months. Fourteen eyes of 12 patients were available for the 12-month follow-up; patients demonstrated improvement in best-corrected visual acuity (difference: -0.21 LogMAR, 95% CI -0.33 to -0.09; P = 0.003), AC cell (OR = 0.10, 95% CI 0.02-0.41; P = 0.002), and IOP (difference: -4.21 mm Hg, 95% CI -7.98 to -0.44; P = 0.03) compared with baseline. One patient experienced a serious adverse event likely due to valganciclovir. Thirteen eyes experienced recurrence of inflammation: 7 (54%) on prophylactic dose of valganciclovir and 6 (46%) after stopping., Conclusions: Valganciclovir appears effective and safe for treating CMVAU in this retrospective case series. Long-term antiviral prophylaxis does not abolish recurrences, although it may possibly reduce their frequency when compared with no prophylaxis.