Because a pregnancy can be achieved without a male infertility evaluation, some have questioned its usefulness. However, by bypassing a urological evaluation the man might not learn the cause of infertility and not be offered specific corrective therapy. In addition, men with subfertility may have a serious underlying medical or genetic problem that could also be overlooked. We determine the incidence of significant medical pathology discovered during a male infertility evaluation at 2 academic infertility practices. All men examined for either primary or secondary infertility were included in our study, while men seen for vasectomy reversal were not. All patients underwent evaluation, consisting of a complete history, physical examination, semen analysis, hormone testing, urinalysis and genetic testing when appropriate. Significant medical pathology was discovered in 33 of 536 (6%) patients. A total of 27 patients had genetic abnormalities, including cystic fibrosis mutations in 24 and karyotypic abnormalities in 3. Of the remaining 6 patients 1 had testis cancer, 1 prostate cancer, 3 diabetes mellitus and 1 hypothyroidism. Significant medical pathology can be detected by a male infertility evaluation. In addition to identifying the cause of infertility, the evaluation may uncover conditions that threaten the health of the male partner or any potential offspring.