OBJECTIVES: The long-term use of esomeprazole, a commonly prescribed proton pump inhibitor, has been associated with a decrease in sperm count and motility, as well as infertility in recent studies. We aimed to present the case of reversible azoospermia developed due to the use of esomeprazole in this study. CASE REPORT: In our study, we examined a 25-year-old unmarried male patient with a desire for children who had been using esomeprazole (40 mg/day) for approximately two years due to gastroesophageal reflux disease. The patient presented to our clinic intermittently with a dull scrotal pain, which was present in both testicles and resolved spontaneously after a short period. The physical examination of the patient revealed no pathological findings, and the testicular volumes and serum hormone parameters were within the normal reference values. The result of scrotal color doppler ultrasound performed on the patient in an external center was reported as scrotal color doppler ultrasound examination within normal limits. Upon the initial presentation of the patient, the semen analysis reported azoospermic pellet positivity. Subsequently, a repeat semen analysis was requested from the patient at a 4-week interval, and the result was once again reported as azoospermic pellet positive. As a result, we discontinued the use of esomeprazole for the patient, and during the first and fourth-month follow-ups, there was a gradual improvement in sperm parameters. The semen analysis parameters evaluated in the fourth month were observed within the normal reference values. CONCLUSIONS: We aimed to emphasize the necessity of considering the use of esomeprazole, which is frequently preferred for gastrointestinal system disorders in our country, as a potential etiology of azoospermia, in a young patient who had been using it for a long time and experienced improvement after discontinuation of the medication. Keywords: azoospermia, esomeprazole, infertility