Polycystic ovary syndrome, the most common cause of irregular menstrual cycles, is associated with an adverse cardiovascular risk profile. However, there are limited prospective studies confirming the link between polycystic ovary syndrome and cardiovascular mortality.We studied 15,005 pregnant women recruited from the Kaiser Foundation Health Plan in California between 1959 and 1966. The menstrual cycle pattern was assessed at baseline according to self-report, physician report, and medical record abstraction. Participants were matched to California Vital Status files annually until 2007 to identify deaths due to overall cardiovascular disease (CVD) and subsets of coronary heart disease (CHD) and cerebrovascular disease based on International Classification of Diseases codes. Cox proportional hazards models were used to estimate the association between irregular cycles and cardiovascular mortality. Missing covariate data were multiply imputated using standard methods.During 456,298.5 person-years of follow-up, there were 666 CVD deaths, including 301 CHD deaths and 149 cerebrovascular deaths. Compared with women with regular cycles, women with irregular cycles had an increased risk for CHD mortality [age adjusted hazards ratio (HR) 1.42, 95% confidence interval (CI) 1.03-1.94]; however, the association was not statistically significant after adjustment for body mass index (adjusted HR 1.35, 95% CI 0.98-1.85). There was a nonsignificant increase in CVD mortality (age adjusted HR 1.21, 95% CI 0.97-1.52) but not cerebrovascular mortality (age adjusted HR 0.85, 95% CI 0.49-1.47).In this large prospective cohort of pregnant women, we found an increase in age-adjusted risk for CHD mortality in women with irregular menstrual cycles. This risk was attenuated after adjustment for body mass index.