We assessed the association of hormonal replacement therapy with mortality and incidence of multiple diseases in over 40,000 postmenopausal women followed for 6 years as part of the Iowa Women's Health Study. Compared with women who never used hormone replacement therapy, current users had multivariate adjusted relative risks (RR) as follows: total mortality (RR = 0.78; 95% confidence interval [CI] = 0.65, 0.94), coronary heart disease mortality (RR = 0.74; 95% CI = 0.48, 1.12), endometrial cancer incidence (RR = 4.3; 95% CI = 2.7, 6.9), breast cancer incidence (RR = 1.23; 95% CI = 0.99, 1.55), colon cancer incidence (RR = 0.72; 95% CI = 0.46, 1.12), and hip fracture incidence (RR = 0.53; 95% CI = 0.31, 0.91).