: ObjectiveTo determine the efficacy of L-carnitine therapy in selected cases of male factor infertility.: DesignPlacebo-controlled, double-blind, crossover trial.: SettingUniversity tertiary referral center.: Patient(s)One hundred infertile patients (ages 20–40 years) with the following baseline sperm selection criteria: concentration, 10–20 × 106/mL; total motility, 10%–30%; forward motility, <15%; atypical forms, <70%; velocity, 10–30 μ/s; linearity, <4. Eighty-six patients completed the study.: Intervention(s)Patients underwent L-carnitine therapy 2 g/day or placebo; the study design was 2 months of washout, 2 months of therapy/placebo, 2 months of washout, and 2 months placebo/therapy.: Main outcome measure(s)Variation in sperm parameters used in the patients selection criteria, in particular, sperm motility.: Result(s)Excluding outliers, a statistically significant improvement in semen quality, greater than after the placebo cycle, was seen after the L-carnitine therapy for sperm concentration and total and forward sperm motility. The increase in forward sperm motility was more significant in those patients with lower initial values, i.e., <5 × 106 or <2 × 106 of forward motile sperm/ejaculate or sperm/mL.: Conclusion(s)Based on a controlled study of efficacy, L-carnitine therapy was effective in increasing semen quality, especially in groups with lower baseline levels. However, these results need to be confirmed by larger clinical trials and in vitro studies. [Copyright &y& Elsevier]