CONTEXT: Obesity, typically measured as body mass index of 30 or higher, has 3 subclasses: obesity 1 (30-34.9); obesity 2 (35-39.9); and extreme obesity (> or =40). Extreme obesity is increasing particularly rapidly in the United States, yet its health risks are not well characterized. OBJECTIVE: To determine how cardiovascular and mortality risks differ across clinical weight categories in women, with a focus on extreme obesity. DESIGN, SETTING, AND PARTICIPANTS: We examined incident mortality and cardiovascular outcomes by weight status in 90,185 women recruited from 40 US centers for the Women’s Health Initiative Observational Study and followed up for an average of 7.0 years (October 1, 1993 to August 31, 2004). MAIN OUTCOME MEASURES: Incidence of mortality, coronary heart disease, diabetes, and hypertension. RESULTS: Extreme obesity prevalence differed with race/ethnicity, from 1% among Asian and Pacific Islanders to 10% among black women. All-cause mortality rates per 10,000 person-years were 68.39 (95% confidence interval [CI], 65.26-71.68) for normal body mass index, 71.16 (95% CI, 67.68-74.82) for overweight, 84.47 (95% CI, 78.90-90.42) for obesity 1, 102.85 (95% CI, 92.90-113.86) for obesity 2, and 116.85 (95% CI, 103.36-132.11) for extreme obesity. Analyses adjusted for age, smoking, educational achievement, US region, and physical activity levels showed that weight-related risk for all-cause mortality, coronary heart disease mortality, and coronary heart disease incidence did not differ by race/ethnicity. Adjusted analyses among white and black participants showed positive trends in all-cause mortality and coronary heart disease incidence with increasing weight category. Much of the obesity-related mortality and coronary heart disease risk was mediated by diabetes, hypertension, and hyperlipidemia. In white women, weight-related all-cause mortality risk was modified by age, with obesity conferring less risk among older women. CONCLUSIONS: Considering obesity as a body mass index of 30 or higher may lead to misinterpretation of individual and population risks. Escalating extreme obesity may exacerbate health effects and costs of the obesity epidemic.