Background Moderate alcohol consumption has been associated with a lower risk of cardiovascular disease (CVD) and all-cause mortality compared with heavy drinkers and abstainers. To date, studies have relied on self-reported consumption, which may be prone to misclassification. Urinary ethyl glucuronide (EtG) is an alcohol metabolite and validated biomarker for recent alcohol consumption. We aimed to examine and compare the associations of self-reported alcohol consumption and EtG with CVD and all-cause mortality. Methods and Results In 5676 participants of the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study cohort, EtG was measured in 24-hour urine samples and alcohol consumption questionnaires were administered. Participants were followed up for occurrence of first CVD and all-cause mortality. Cox proportional hazards regression models, adjusted for age, sex, and CVD risk factors, were fitted for self-reported consumption, divided into 5 categories: abstention, 1 to 4 units/month (reference), 2 to 7 units/week, 1 to 3 units/day, and ≥4 units/day. Similar models were fitted for EtG, analyzed as both continuous and categorical variables. Follow-up times differed for CVD (8 years; 385 CVD events) and all-cause mortality (14 years; 724 deaths). For both self-reported alcohol consumption and EtG, nonsignificant trends were found toward J-shaped associations between alcohol consumption and CVD, with higher risk in the lowest (hazard ratio for abstention versus 1-4 units/month, 1.42; 95% CI, 1.02-1.98) and highest drinking categories (hazard ratio for ≥4 units/day versus 1-4 units/month, 1.11; 95% CI, 0.68-1.84). Neither self-report nor EtG was associated with all-cause mortality. Conclusions Comparable associations with CVD events and all-cause mortality were found for self-report and EtG. This argues for the validity of self-reported alcohol consumption in epidemiologic research.