Background: It has not been well established whether common indices of male condom failure are valid predictors of biologically meaningful exposure during condom use. Methods: To address this gap, the authors compared self-reported condom malfunctions (i.e., breakage and slippage) and incorrect condom practices to 2 following objective measures of failure: prostate-specific antigen (PSA) detected in vaginal swabs collected after condom use and structural integrity of used condoms. The study, conducted in 2000-2001, evaluated 635 male condoms used by 77 women attending an outpatient, reproductive-health clinic in Birmingham, AL. Results: Women reported breakage or slippage for 7.9% of condoms; 3.5% of postcoital swabs had moderate or high levels of PSA; and laboratory testing of used condoms revealed breaks (1.1%) and leaks (2.0%). Self-reported breakage and slippage was associated with moderate/high PSA concentrations in postcoital swabs only when the malfunctions were not accompanied by reports of corrective actions to reduce exposure (adjusted odds ratio [aOR], 6.9; 95% confidence interval [CI], 1.8-26.2). Defects observed in postcoital laboratory testing were related to PSA detection (aOR, 8.0; 95% CI, 1.5-42.6). Incorrect practices defined on the condom label were frequent, but not all types were associated with semen exposure. Furthermore, other practices not currently label-defined were associated with semen exposure: touching the tip of the penis with his hands (aOR, 6.2; 95% CI, 2.3-17.0) or with her hands (aOR, 2.8; 95% CI, 1.1-72) before donning the condom. Conclusions: Used correctly, male condoms afforded good protection based on objective measures of failure. © 2011 American Sexually Transmitted Diseases Association All rights reserved.