Purpose of investigation: Few studies have been conducted to investigate drug effects on spontaneous abortion risk. The objective of the present study was to evaluate the potential association between first trimester drug exposure and spontaneous abortion occurrence. Materials and Methods: The authors performed a nested case-control study using data from TERAPPEL, a French medical database. Cases were the women who had a spontaneous abortion (before the 22^nd week of amenorrhea) and controls were women who gave birth to a child. Analyzed variables were: maternal age, obstetric history, tobacco, and alcohol and drug consumption during the first trimester of pregnancy. For comparison of drug exposures between cases and controls, the authors calculated odds ratios (ORs) by means of multivariate logistic regressions adjusted on age and on other drug exposures. Results: The study included 838 cases and 4,508 controls that were identified in the database. In adjusted analyses, cases were more exposed than controls to “non-selective monoamine reuptake inhibitors” [OR=2.2 (CI95% 1.5-3.3)], “anti-protozoals” [OR = 1.6 (CI 95% 1.1 - 2.5)] and “centrally acting anti-obesity products” [OR = 3.4 (CI 95% 1.9 - 6.2)]. Conversely, controls were more exposed than cases to H1 antihistamines [OR = 0.6 (CI 95% 0.4 - 0.9)]. Conclusion: This exploratory study highlights some potential associations between first trimester drug exposure and risk of spontaneous abortion. Further studies have to be carried out to investigate these findings.