Purpose: To evaluate the safety and kinetics of prophylactic intracameral cefuroxime in cataract surgery. Setting: Department of Ophthalmology, St. Eriks Hospital, Stockholm, Sweden. Methods: In a nonrandomized observer-masked best-case trial, the visual rehabilitation and the evolution of laser flare intensity and corneal endothelial cell density after cataract surgery were assessed in 45 patients receiving intracameral cefuroxime and in 45 control patients. Immunoglobulin E-mediated sensitivity was evaluated using a skin prick test to cefuroxime in a screening program comprising all cataract patients operated on in 1997. Intracameral concentrations of cefuroxime in samples retrieved 30 seconds (n = 10) and 1 hour (n = 9) postoperatively were evaluated in an observer-masked fashion with a microbiological assay. Results: Intracameral cefuroxime did not have a statistically significant effect on postoperative visual acuity, induced laser flare intensity, or endothelial cell loss compared with nonadministration of intracameral antibiotic prophylaxis. Three positive skin prick tests to cefuroxime were found in the 5813 screened cataract patients. The median aqueous humor concentration of cefuroxime at 30 seconds was 2742 mg/L, declining to 756 mg/L 1 hour after drug instillation. Conclusions: Intracameral cefuroxime 1 mg appears safe in terms of local toxicity. Immunoglobulin E-mediated allergy to cefuroxime is rare in the cataract population. The treatment achieved high aqueous concentrations even 1 hour after surgery.