To gain further knowledge of possible risk factors for the development of postoperative endophthalmitis (POE) following cataract surgery, a single-centre retrospective case–control study was conducted for 1994–2000. In total, 46292 cataract procedures were performed during the study period. Sixty cases of POE were noted and 240 control cases were selected at random. Parameters pertaining to patient history and to peri-operative technique and complications were analysed. The relative risk of POE was calculated using univariate analyses and multi-variate forward stepwise logistic regression. In the logistic regression analyses, three statistically significant parameters were found. The use of intracameral prophylaxis with cefuroxime as opposed to topical treatment alone, and performing phaco-emulsification instead of extra- or intracapsular cataract extraction appeared to be protective against POE. Silicone intra-ocular lenses carried a higher risk than heparin surface modified poly (methyl methacrylate) implants. In summary, the important finding of this study was the protective effect against POE of intracameral prophylaxis with cefuroxime compared with topical anti-infectives alone.