PURPOSE: To compare the five-year incidence of acute post-operative endophthalmitis following cataract surgery, between centers with and without laminar air flow and high-efficiency particulate air (HEPA) filters in operating rooms. METHODS: Retrospective analysis of medical records of patients operated in a single network of a tertiary and four secondary hospitals across north India. Cases of endophthalmitis were identified from the records between January 2013 and June 2018. Protocols and consumables were standardized across all hospitals. The only infrastructural difference being the presence of laminar air flow and high energy particulate air filters in operating rooms of the tertiary center. The type of surgery, along with the demographic and socio-economic details, were captured and analyzed, using z-test for proportions and logistic regression. RESULTS: Out of 88,297 cataract surgeries conducted, 36 cases of endophthalmitis were reported. The incidence of endophthalmitis across the network was estimated to be 0.041%, (95% CI: 0.027 to 0.054). There was no statistically significant difference between the incidence of POE at the tertiary (0.042%) and secondary centers (0.039%). Certain risk factors for high endophthalmitis incidence were identified, namely patients undergoing small incision cataract surgery and belonging to lower socio-economic status. However, for both factors the difference was not statistically significant. CONCLUSION: The five-year incidence of acute post-operative endophthalmitis in our network was found comparable to the best reported in literature. Incidence at secondary centers, without laminar air flow and high energy particulate air filters was found comparable to that in the tertiary center having these facilities.