Nausea and vomiting are very common during pregnancy, mainly throughout the first trimester. Metoclopramide is a dopamine receptor blocking drug that is commonly used to treat nausea and vomiting. The aim of this prospective study was to investigate the effect on the fetus of intrauterine exposure to metoclopramide. One hundred and seventy-five women who received metoclopramide and consulted 6 teratogen information centers in Israel, Italy, Brazil, and Canada were studied. Women exposed to metoclopramide were paired for age, smoking and alcohol consumption habits with women exposed to nonteratogens. Women in the metoclopramide group had a significantly higher rate of premature births (8.1%) as compared with the control group (2.4%) ( p = 0.02, relative risk = 3.37, 95% confidence interval 1.12-10.12). Rates of major malformations in the metoclopramide group (4.4%) did not differ from controls (4.8%) ( p = 0.84, relative risk = 0.91, 95% confidence interval 0.34-2.45). According to our findings, metoclopramide use during the first trimester of pregnancy does not appear to be associated with an increased risk of malformations, spontaneous abortions, or decreased birth weight, however, larger studies are needed to confirm these observations.