OBJECTIVE: The purpose of this study was to examine prepregnancy cardiometabolic and inflammatory markers and the subsequent risk of hypertensive disorders of pregnancy. STUDY DESIGN: This was a retrospective cohort study of 3380 women who took part in a comprehensive multiphasic health checkup (MHC) examination between 1984 and 1996 and who subsequently delivered at Kaiser Permanente Northern California. RESULTS: Two hundred five women were diagnosed with a hypertensive disorder of pregnancy. Prepregnancy measurements of overweight/obesity (body mass index, >/=25.0 kg/m(2)), prehypertension, and inflammation (leukocytes, >/=7.2 10(3)/muL) were associated independently with hypertensive disorder of pregnancy risk (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2-2.3; OR, 2.1; 95% CI, 1.5-2.8; and OR, 1.6; 95% CI, 1.1-2.3, respectively). Being overweight/obese and having prehypertension before pregnancy was associated with a 3.5-fold increased risk of hypertensive disorder of pregnancy compared with women with normal levels of both risk factors. CONCLUSION: A prepregnancy cardiometabolic and inflammation risk profile may help clinicians identify high-risk women to target for early intervention or management of hypertensive disorder of pregnancy.