There are few data on the effects of methotrexate on reproductive capacity in men with inflammatory bowel diseases (IBD). We performed a case–control study to determine the effects of methotrexate on sperm quality and genetic integrity. We compared sperm samples from 7 men with IBD who had been exposed to methotrexate for at least 3 months with sperm samples collected from 1912 age-matched men at fertility centers (controls), where sperm parameters would be expected to be worse than those of the general population.