Evidence suggests that work schedule, including rotating work and night work, may have an adverse effect on reproductive outcome, but results from these studies are ambiguous, and there are few studies of U.S. health care workers. We examined this question among 7,683 female participants of the Nurses Health Study II, a prospective cohort established in 1989. In 2001, detailed information abut specific exposures during pregnancy was collected from participants for the most recent pregnancy they had experienced since 1993. Participants reported 6,897 live births and 786 (10%) spontaneous abortions (SA). Log binomial regression was used to estimate the relative risk (RR) for SA, adjusting for potentail confounders. Compared to women who reported usually working "days only" during their first trimester of pregnancy, women who reported working more than 40 hours per week during the first trimester were also at increased risk of SA (RR=1.5, 95% CI 1.3-1.8) compared to women who reported working 21-40 hours per week, even after adjustment for work schedule. Hormonal disturbances, either as a direct effect of circadian rhythm disruption or indirectly through work-related stress and altered sleep pattterns, may be a possible interpretation of these findings.