Purpose: We aimed to evaluate the effect of testosterone replacement therapy (TRT) on cognitive function and depression in men with testosterone deficiency syndrome. Materials and Methods: We carried out a prospective, placebo-controlled trial involving 106 men with total testosterone levels0.05). At baseline, no significant differences between the TRT and control groups were noted regarding serum testosterone or prostate-specific antigen levels, or regarding the scores for aging symptoms (Aging Males' Symptoms scale), erectile function (5-item International Index of Erectile Function questionnaire), cognitive function (Korean Mini-Mental State Examination), and depression (Beck Depression Inventory). At 8 months after intervention total serum testosterone levels and erectile function scores had significantly increased (p<0.05), whereas the scores for aging symptoms and depression had significantly decreased (p<0.05) in the TRT group; no significant improvement in any parameters was noted for the control group. Notably, significant improvement in cognitive function was noted among patients with cognitive impairment at baseline (cognitive function score <25) who received TRT. Conclusions: TRT may be considered in men with testosterone deficiency syndrome if low testosterone levels are associated with depression or cognitive impairment.