BACKGROUND Hormonal male contraceptive regimens effectively and reversibly suppress sperm production, but there are few large-scale efficacy studies. OBJECTIVE The safety, contraceptive efficacy, reversibility, and feasibility of injectable testosterone undecanoate (TU) in tea seed oil as a hormonal male contraceptive was assessed. METHODS This was a multicenter, phase III, contraceptive efficacy clinical trial. METHODS A total of 1045 healthy fertile Chinese men were recruited throughout China into the study. METHODS Injections of 500 mg TU were administered monthly for 30 months. A definition of severe oligozoospermia (< or =1 x 10(6)/ml) was used as a criterion of spermatogenic suppression and as the threshold for entering the contraceptive efficacy phase. METHODS The primary outcome was pregnancy rate in the partner. Other outcomes include: semen parameters, testis volumes, reproductive hormone levels, and safety laboratory tests. RESULTS Forty-three participants (4.8%) did not achieve azoospermia or severe oligozoospermia within the 6-month suppression phase. A total of 855 participants entered into the efficacy phase, and 733 participants completed monthly TU treatment and follow-up. There were nine pregnancies in 1554.1 person-years of exposure in the 24-month efficacy phase for a cumulative contraceptive failure rate of 1.1 per 100 men. The combined method failure rate was 6.1%, comprising 4.8% with inadequate suppression and 1.3% with postsuppression sperm rebound. No serious adverse events were reported. Spermatogenesis returned to the normal fertile reference range in all but two participants. CONCLUSIONS Monthly injection of 500 mg TU provides safe, effective, reversible, and reliable contraception in a high proportion of healthy fertile Chinese men.