© 2014, Society of General Internal Medicine. BACKGROUND: Data are limited regarding the influence of diet drink consumption on cardiovascular disease (CVD) outcomes. OBJECTIVE: We aimed to evaluate the relationship between diet drink intake and cardiovascular events. DESIGN: We conducted a retrospective cohort study, utilizing data from the national, multicenter Women’s Health Initiative Observational Study (WHI OS), recruiting subjects from 1993 to 1998. PATIENTS: Post-menopausal women with available diet drink intake data, without pre-existing CVD and who survived ≥ 60 days were included in the study. MAIN MEAURES: A composite of incident coronary heart disease, heart failure, myocardial infarction, coronary revascularization procedure, ischemic stroke, peripheral arterial disease and CVD death was used as the primary outcome. CVD death and all-cause mortality were secondary outcomes. Adjusted Cox proportional hazards models were used to compare primary and secondary outcomes across diet drink intake strata. KEY RESULTS: In all, 59,614 women, mean age 62.8 years, were included for analysis. In unadjusted analysis over a follow-up of 8.7 ± 2.7 years, the primary outcome occurred in 8.5 % of the women consuming ≥ 2 diet drinks/day, compared to 6.9 %, 6.8 % and 7.2 % in the 5–7/week, 1–4/week and 0–3/month groups, respectively. After controlling for other CVD risk factors, women who consumed ≥ 2 drinks/day had a higher adjusted risk of CVD events (HR 1.3, 95 % CI 1.1–1.5), CVD mortality (HR 1.5, 95 % CI 1.03–2.3) and overall mortality (HR 1.3, 95 % CI 1.04–1.5) compared to the reference group (0–3 drinks/month). CONCLUSIONS: This analysis demonstrates an association between high diet drink intake and CVD outcomes and mortality in post-menopausal women in the WHI OS.