The association between HRT and CVD incidence and mortality, as well as CAD and stroke incidence and mortality, is uncertain, based on conflicting findings, and limited by lack of randomization and consequent selection biases among women using HRT in the observational studies. Our meta-analysis differs from prior meta-analyses by evaluating potential explanatory variables of the HRT-CVD/CAD relationship, as well as different measures of HRT exposure. It shows a small decrease in CVD and CAD deaths only among current HRT users and no effect on stroke, and suggests that SES, alcohol use, and exercise are important confounders of the HRT/CVD/CAD relationship. A valid answer to the potential role of HRT in the primary prevention of CVD will best come from randomized controlled trials.