A retrospective case-control study of patients who had undergone cataract extraction at a Spanish hospital over a 13-year period was conducted to identify the risk factors for developing post-operative endophthalmitis (POE). During the study period, the type of antibiotic prophylaxis was changed from subconjunctival gentamicin to the addition of both vancomycin and gentamicin to the irrigating solution. The overall incidence of POE was 0·19% (35 cases/18 287 operations). For the period prior to the change in antibiotic prophylaxis, the incidence rate of POE was 3·4 cases/1000 operations while in the latter period the incidence rate decreased to 0·34 cases/1000 operations. All patients who presented a virulent microorganism had a final visual acuity worse than 20/200. The only significant risk factor identified was the type of prophylaxis used (odds ratio 1·97, 95% confidence interval 0·94-4·14, P = 0·07). There were no significant differences between cases and controls although choice of surgeon approached significance.