ObjectiveTo investigate the contributions of ovulation-inducing drugs and assisted reproductive technologies to multiple birth.MethodsThis historic prospective study was conducted in a cohort of 13,151 women who delivered after 20 weeks' gestation between October 1996 and December 1999. The study setting was a Colorado health maintenance organization. Cases were women who were pregnant as a result of exposure to treatment with either assisted reproductive technologies or ovulation induction in the absence of assisted reproductive technologies. The main outcome measure was multiple birth.ResultsThere was a significant association between assisted conception and multiple birth. Compared with women with naturally conceived pregnancies, there was a 25-fold likelihood (95% confidence interval 18, 35,P< .001) of multiple birth among women exposed to any of those treatments. In the total cohort the proportion of multiple births attributable to those treatments was 33%. After adjusting for the use of assisted conception and other covariates, we found no association between advanced maternal age and multiple birth.ConclusionIn this cohort, assisted reproductive interventions were strongly associated with multiple birth. Although a higher proportion of older women sought assisted reproductive technologies, we did not find an independent relationship between advanced maternal age and multiple birth. The increasing number of multiple births attributable to assisted conception raises public health concerns regarding multiple gestation-related maternal and infant morbidities.