AIM: To determine the risk factors for acute endophthalmitis after cataract extraction in a tertiary care centre in India. METHODS: We performed a nested case control study within a retrospective cohort. The surgical records of all patients with clinically diagnosed endophthalmitis within one month after cataract surgery, performed between January 2006 and December 2009, were reviewed. These were compared with randomly selected age and gender-matched controls, from patients having routine cataract surgery within ±1wk of the endophthalmitis case. Univariable and multivariable analysis were performed to identify risk factors for endophthalmitis. RESULTS: Of the total 33 856 cataract surgeries performed during this period, there were 57 cases of postoperative acute endophthalmitis that met our study criteria. Thus, the overall incidence of endophthalmitis in our cohort was 1.6 per 1000 cataract extractions performed. Mean age of cases was 55.9y (SD: 10.9y) and for controls was 55.6y (SD: 9.8y). Thirty-five cases (61.4%) and 133 controls (59.6%) were males. Median time of onset of endophthalmitis was 4d (IQR 2-9d; range: 1-30d). Thirty-nine cases (68.4%) presented within 7d and 27 cases (47.4%) were culture positive. Two hundred and twenty-three age and gender matched controls were selected. In multivariate analysis, endophthalmitis was associated with posterior capsular rupture (PCR) during surgery (OR 6.98, 95%CI: 2.22-21.98), phacoemulsification via scleral incision with a foldable intraocular lens (IOL) implantation (OR 3.02, 95%CI: 1.13-8.04) and ocular co-morbidity (OR 2.32, 95%CI: 1.11-4.87). CONCLUSION: PCR, presence of ocular co-morbidity, and phacoemulsification via scleral incision with foldable-IOL were found to be independent risk factors for acute endophthalmitis.