The purpose of this study was to determine the association between male occupational exposures and infertility. A retrospective case-control study was performed using data collected between 1991 and 1997 at nine US clinical sites as part of a previously conducted large multicenter trial. Cases were defined as infertile males whose partner had an infertility evaluation with normal results, and controls were defined as fertile males whose partner became pregnant within 2 years. Exposures were assessed by means of self-report questionnaires. Bivariate, stratified, and multivariable analyses were performed. A total of 650 infertile cases and 698 fertile controls were compared. In the final model, a protective association with infertility was observed for occupational exposures to radiation (odds ratio=0.21, 95% confidence interval: 0.06, 0.77) and video display terminals (odds ratio=0.30, 95% confidence interval: 0.13, 0.68). No significant associations were noted between infertility and exposure to shift work, metal fumes, electromagnetic fields, solvents, lead, paint, pesticides, work-related stress, or vibration. Overall, no clear, clinically important associations between occupational exposures and male infertility could be identified in this study.