The aim of this study was to compare fibulin-5 expression in women with and without anterior vaginal wall prolapse. Vaginal tissues were sampled in a standardized fashion from women with (n = 12) or without (n = 10) anterior vaginal wall prolapse. Quantitative real-time polymerase chain reaction was performed to measure mRNA levels of fibulin-5 (FIB-5). FIB-5 protein expression was assessed by immunohistochemistry. There were no significant differences in demographic data between the two groups. FIB-5 mRNA expression was significantly decreased in women with anterior vaginal wall prolapse compared to women without prolapse [(FIB-5 mean +/- SD mRNA expression in relative units) 0.01 +/- 0.01 vs. 0.09 +/- 0.14, P = 0.04]. Fibulin-5 staining intensity was diminished in women with prolapse compared to women without prolapse [intensity score, median (range), 1 (1-2) vs. 3 (2-3), P = 0.04]. Fibulin-5 expression is decreased in vaginal biopsies from women with prolapse. Changes in fibulin expression may play a role in the development of pelvic organ prolapse.