To identify patient-specific factors predictive of maintenance warfarin dosage requirements >5 mg/d. One hundred forty-six adults taking warfarin were identified from a community hospital and an outpatient anticoagulation clinic. Patient demographics and data on warfarin doses, laboratory results, and medication use were obtained by abstracting patient records. Estimates of vitamin K intake were obtained using a questionnaire and structured interview. Multiple logistic regression was used to identify patient characteristics independently predictive of warfarin maintenance requirements >5 mg/d. An assessment tool for estimating an individual patient's likelihood of requiring warfarin maintenance doses >5 mg/d was derived from the logistic regression model and was assessed in both the study cohort and a separate historical validation cohort of 125 patients. Five factors were independently associated with warfarin requirements >5 mg/d: age <55 years, male gender, African American ethnicity, vitamin K intake >400 micro g/d, and body weight >or=91 kg. The assessment tool derived from these factors correctly classified semiquantitative warfarin requirements as non-high-dose in 84 of 93 study cohort patients and 71 of 78 validation cohort patients, and correctly classified requirements as high-dose in 10 of 13 study cohort patients and 11 of 15 validation cohort patients. African American ethnicity is a newly identified predictor of warfarin requirements >5 mg/d and is independent of dietary vitamin K intake. An assessment tool incorporating this and other predictors can estimate a patient's likelihood of requiring such dosages.