We report the clinical features, microbiological profile, and outcomes in 45 cases of endophthalmitis following 111,876 vitrectomies performed over a period of 20 years. The incidence of clinically evident and culture-proven endophthalmitis after 20G vitrectomy was 5.7 and 3.1 cases per 10,000 surgeries, respectively. Previous studies have shown varied incidences with 20-G vitrectomy: 7 cases per 10,000 surgeries in earlier studies and reducing to 2 cases per 10,000 surgeries reported in the later studies.[2–10]