Objective: Premature uterine contractions represent one of the major symptoms related to preterm labor. So far, primary prevention of preterm labor is based on the early identification of symptoms and on pharmacological treatments which are prone of several secondary effects. In this double-blinded, randomized, placebo-controlled trial, the efficacy of a supplementation of magnesium and alpha-lipoic acid has been evaluated. Methods: Three hundred pregnant women at 14 - 34 weeks of gestation were enrolled and randomly divided to receive a daily single tablet containing a supplement of magnesium and alpha-lipoic acid (DAV®LoLiPharmasrl, Rome-Italy) or placebo until delivery. The incidence of episodes of preterm uterine contraction, associated or not with pain, as well as maternal need of hospitalization was evaluated. Results: Magnesium and lipoic acid supplementation was effective to significantly reduce the incidence of preterm uterine contractions compared to placebo. In particular, 52% of women who received the supplementation reported no symptoms of preterm uterine contractions throughout pregnancy, and persistent episodes of uterine contractions were significantly reduced compared to placebo (20% vs 60%, respectively). Furthermore, only 20% of subjects who received the supplementation required hospitalization, while it has been necessary for 40% of women who received placebo. Conclusions: Our findings suggest that supplementation with magnesium and lipoic acid is effective in reducing the incidence of premature uterine contraction and related episodes of hospitalization, compared to placebo. Nevertheless, further studies based on larger cohorts of patients are necessary to confirm the efficacy of these preliminary results.