OBJECTIVES To identify patient groups associated with a high probability of false positives in photodynamic diagnosis (PDD) of bladder cancer for which the use of highly specific optical instruments Could be beneficial. METHODS This study includes the data of 306 patients. Under white light and 5-aminolevulinic acid-induced fluorescence light guidance, tumor locations were recorded, cold-cup biopsies were taken and tumors resected. Age, gender, recent transurethral resection of bladder tumor (TURBT), previous intravesical therapy, and urinary tract infections were examined for association with the false-positive rates in fluorescence cystoscopy by performing a multivariate analysis. RESULTS Significant univariate associations were found between false positives and gender (P = .009, odds ratio [OR] = 0.51), previous intravesical therapy (P = .03, OR = 1.78), previous BCG instillations (P = .03, OR = 2.05), and TURBT in the past 90 days (P = .01, OR = 2.37). In the multivariate regression model, female gender (male; P = .005, OR = 0.41) and TURBT within 90 days before PDD (P = .01, OR = 2.38) are significant independent predictors of false-positive findings in PDD. CONCLUSIONS Recent TURBTs and female gender are significant independent predictors of false positives in fluorescence cystoscopy. UROLOGY 74: 851-857, 2009. (C) 2009 Elsevier Inc.