BACKGROUND: Adverse drug events are an important cause of preventable hospitalizations. OBJECTIVE: To identify whether patient report of receipt of medication instructions and markers of complex care (multiple physicians, recent hospitalization) predict the risk of serious bleeding for older adults on warfarin. DESIGN: Prospective cohort study of older adults. PARTICIPANTS: Subjects filled new or refill prescriptions for warfarin at the time of enrollment. MEASUREMENTS: Hospitalizations were identified through a state-wide registry. Discharge summaries of hospitalizations for possible warfarin related bleeding events were reviewed by trained abstractors and clinical experts. Incidence rate ratios (IRR) were estimated based on person-months of exposure using Poisson regression models. RESULTS: From March 2002 through May 2003, we enrolled a total of 2346 adults on warfarin. Over a two-year follow-up period, there were 126 hospitalizations due to warfarin-related bleeding (4.6 hospitalizations per 100 person-years of exposure). Patients who reported receiving medication instructions from either a physician or nurse plus a pharmacist had a 60% reduced rate of subsequently experiencing a serious bleeding event over the next 2 years (adjusted IRR 0.40, 95% CI 0.24-0.68). Having > or = 4 physicians providing medication prescriptions over the last 3 months and filling prescriptions at > 1 pharmacy over the last 3 months were independently associated with increased bleeding rates (adjusted IRRs 2.37, 95% CI 1.22-4.57 and 1.61, 95% CI 0.97-2.67, respectively). CONCLUSIONS: The rate of warfarin-related hospitalization for bleeding is substantially lower for patients who report receiving medication instructions from a physician or nurse and a pharmacist.