- Background Spontaneous abortions are the most common complication of pregnancy. Clotrimazole and miconazole are widely used vaginal-antimycotic agents used for the treatment of vulvovaginal candidiasis. A previous study has suggested an increased risk of miscarriage associated with these azoles, which may lead health professionals to refrain from their use even if clinically indicated. Objective The aim of the current study was to assess the risk for spontaneous abortions following first trimester exposure to vaginal antimycotics. Study Design A historical cohort study was conducted including all clinically apparent pregnancies that began from January 2003 through December 2009 and admitted for birth or spontaneous abortion at Soroka Medical Center, Clalit Health Services, Beer-Sheva, Israel. A computerized database of medication dispensation was linked with 2 computerized databases containing information on births and spontaneous abortions. Time-varying Cox regression models were constructed adjusting for mother’s age, diabetes mellitus, hypothyroidism, obesity, hypercoagulable or inflammatory conditions, recurrent miscarriages, intrauterine contraceptive device, ethnicity, tobacco use, and the year of admission. Results A total of 65,457 pregnancies were included in the study: 58,949 (90.1%) ended with birth and 6508 (9.9%) with a spontaneous abortion. Overall, 3246 (5%) pregnancies were exposed to vaginal antimycotic medications until the 20th gestational week: 2712 (4.2%) were exposed to clotrimazole and 633 (1%) to miconazole. Exposure to vaginal antimycotics was not associated with spontaneous abortions as a group (crude hazard ratio, 1.11; 95% confidence interval, 0.96–1.29; adjusted hazard ratio, 1.11; 95% confidence interval, 0.96–1.29) and specifically for clotrimazole (adjusted hazard ratio, 1.05; 95% confidence interval, 0.89–1.25) and miconazole (adjusted hazard ratio, 1.34; 95% confidence interval, 0.99–1.80). Furthermore, no association was found between categories of dosage of vaginal antimycotics and spontaneous abortions. Conclusion Exposure to vaginal antimycotics was not associated with spontaneous abortions.