Previous studies have indicated that nonsteroidal anti-inflammatory drugs, including ibuprofen, may have varying effects on the male reproductive system. This study aimed to evaluate the impact of ibuprofen on male infertility in Taiwan. This nationwide retrospective cohort study used the Taiwan National Health Insurance Database from January 1, 2000, to December 31, 2021. The study participants were males aged 20-59 years who had used ibuprofen or acetaminophen between 2000 and 2020. The primary outcome was the incidence of male infertility. Cox regression analysis estimated cumulative incidences and hazard ratios (HRs) with their corresponding 95 % confidence intervals (CIs). The Kaplan-Meier method was used to illustrate cumulative incidence curves. The participants using ibuprofen and acetaminophen were 11,194 and 11,194. After the propensity score matching, the two groups did not show differences in age, medication year, and disease prevalence. Ibuprofen usage for >60 days per year had a higher HR (2.01, 95 % CI: 1.03-4.01) of male infertility than acetaminophen usage for the same duration. The cumulative incidence of male infertility over time showed that ibuprofen use for >60 days per year was significantly associated with a higher incidence of male infertility compared to acetaminophen (p < 0.001). The association between ibuprofen use and male infertility has broad public health implications. If further confirmed through prospective studies, these findings may impact medical advice and inform discussions on drug use, particularly among individuals of reproductive age.