Among 617 hospitalized patients who started long-term anticoagulant therapy, major bleeding developed before discharge in 28 (5 percent) and minor bleeding in another 38 (6 percent), with daily incidence rates of 0.4 and 0.5 percent, respectively. The most common site of bleeding was gastrointestinal, and one patient died from bleeding. Four independent risk factors for major in-hospital bleeding were identified and weighted using multivariate discriminant analysis in a randomly chosen group of 411 patients: (1) co-morbid conditions other than the indication for anticoagulant therapy (specific signs of heart, liver, or kidney dysfunction, cancer, and severe anemia); (2) the use of heparin to begin therapy in patients age 60 years or older; (3) the intensity of therapy (measured by the maximal prothrombin time or partial thromboplastin time); and (4) liver dysfunction that worsened during treatment. These findings were validated in an independent testing group of 206 patients; the risk factors identified 151 patients at low (1 percent) risk of major bleeding, 33 at moderate (6 percent) risk, and 22 at high (23 percent) risk. The accuracy and clinical impact of this prediction rule should be evaluated further in other hospitals. © 1987.