Purpose We determined the efficacy of coenzyme Q10 supplementation on semen parameters, sperm function and reproductive hormone profiles in infertile men. Materials and Methods A total of 212 infertile men with idiopathic oligoasthenoteratospermia were randomly assigned to receive 300 mg coenzyme Q10 (Kaneka, Osaka, Japan) orally daily (106 in group 1) or a similar placebo regimen (106 in group 2) during a 26-week period, followed by a 30-week treatment-free phase. Two semen analyses, acrosome reaction test, immunobead test for antisperm antibody, and determination of resting levels of luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone and inhibin B were done in all participants. Blood and seminal plasma total coenzyme Q10 was also assessed. Results Significant improvement in sperm density and motility was evident with coenzyme Q10 therapy (each p = 0.01). Using the Kruger classification sperm morphology evaluation revealed an increase in the percent of normal forms in the coenzyme Q10 group (p = 0.07). A positive correlation was found between treatment duration with coenzyme Q10 and sperm count (r = 0.46, p = 0.03) as well as with sperm motility (r = 0.45, p = 0.04) and sperm morphology (r = 0.34, p = 0.04). The coenzyme Q10 group had a significant decrease in serum follicle-stimulating hormone and luteinizing hormone at the 26-week treatment phase (each p = 0.03). By the end of the treatment phase the mean ± SD acrosome reaction had increased from 14% ± 8% and 15% ± 8% to 31% ± 11% and 16% ± 10% in the coenzyme Q10 and placebo groups, respectively (p = 0.01). Conclusions Coenzyme Q10 supplementation resulted in a statistically significant improvement in certain semen parameters. However, further studies are needed to draw a final conclusion and evaluate the effect of coenzyme Q10 supplementation on the pregnancy rate.