A major misperception concerning postmenopausal hormone replacement therapy (HRT) is that the associated risks are large in magnitude and unique to HRT, but over the past 10 years, sufficient data have accumulated so that the magnitude and perspective of risks associated with the primary coronary heart disease prevention therapies of statins, aspirin, and postmenopausal HRT have become more fully defined. Review of randomized controlled trials indicates that the risks of primary prevention therapies and other medications commonly used in women's health are of similar type and magnitude, with the majority of these risks categorized as rare to infrequent (<1 event per 100 treated women). Evidence-based data show that the risks of postmenopausal HRT are predominantly rare (<1 event per 1,000 treated women) and certainly no greater than other commonly used medications in women's health, including statins and aspirin. These risks, including breast cancer, stroke, and venous thromboembolism are common across medications and are rare, and even rarer when HRT is initiated in women younger than 60 or who are less than 10 years since menopause. In Part 1 of this series, the sex-specificity of statins and aspirin and timing of initiation of HRT as modifiers of efficacy in women were reviewed. Herein, the comparative risks of primary prevention therapies in women are discussed.