PURPOSE: Long-acting injectable testosterone undecanoate (TU, Nebido(R)), a new parenteral testosterone preparation, has recently been introduced to avoid frequent injections of the conventional injectable esters. We performed this study to assess the efficacy and safety of long-acting injectable TU in patients who suffer with testosterone deficiency syndrome (TDS). MATERIALS AND METHODS: In this prospective, non-controlled single arm trial, a total of 33 patients (a mean age of 55.8+/-6.4 yrs) with TDS, as defined by serum testosterone levels of less than 3.5 ng/mL, were injected with 1000 mg of TU (4mL/ampule) on day 1, followed by another injection 6 weeks later with follow-up injections 3 months thereafter for a total of 54 weeks. Before and 18 and 54 weeks after the TU injections, the changes of the Aging Males' Symptoms (AMS) scale, the serum total testosterone, the lipid profiles, the CBC, the PSA level, the prostate volume by TRUS and the body mass index (BMI) were compared by Students' paired t-tests. Any adverse effects were also evaluated. RESULTS: Compared to the pretreatment results, the serum total testosterone level was significantly increased at 18 and 54 weeks (P<0.01), but there was no difference for the serum total testosterone level between weeks 18 and 54, that is, they were stable. The BMI was not significantly decreased at 54 weeks compared to pretreatment. Injectable TU also significantly improved the AMS scores, and especially in the sexual domain (P<0.01). The other data, except the hematocrit, was not significantly changed (P<0.05). Injectable TU did not show a harmful effect on the prostate during the 54 weeks. No patient reported any adverse side effects or events. CONCLUSIONS: Injectable TU effectively elevated the serum total testosterone levels and it maintained stable concentrations during the treatment period. Injectable TU significantly improved the total AMS score, but there were no reported significant changes in the body habitus and lipid profiles. Further large, well-controlled, long-term studies should be done to assess the effect of injectable TU on TDS patients.