PURPOSE: To investigate whether the use of topical povidone-iodine before surgery, the addition of vancomycin to the irrigating solutions during phacoemulsification, or both reduces the frequency of positive intraocular cultures at the end of surgery, METHODS: A two-part, clinical study was performed, In the preliminary study, intracameral antibiotic concentrations were measured immediately after surgery (in 11 eyes) and 2 hours after surgery (in 11 eyes) in patients treated with vancomycin, In the primary study, 400 patients were divided into four groups composed of 100 eyes each. The first and the second groups received vancomycin (20 mug/ml) in the irrigating fluid, The third and the fourth groups received irrigating fluid only without antibiotics. The first and third groups received a topical 5% povidone-iodine solution 10 and 5 minutes before surgery; a topical placebo solution was used in the second and the fourth groups. All patients in the primary study underwent anterior chamber aspiration after surgery, and culturing was performed 2 hours later. Identification and quantification of positive cultures in thioglycolate broth and chocolate agar were performed. RESULTS: In the preliminary study, the half-life of intraocular vancomycin was less than 2 hours, In the primary study, intraocular aspirates yielded positive cultures in two (2%), five (5%), 11 (11%), and 13 (13%) specimens from the first, second, third, and fourth groups, respectively. CONCLUSIONS: We found a lower rate of positive cultures in the group that received vancomycin in the irrigating fluid; 2 hours of contact between the antibiotic solution and bacteria produced results that reached statistical significance (P = 0.032), (Am J Ophthalmol 2001;131:293-300, (C) 2001 by Elsevier Science Inc, All rights reserved.).