OBJECTIVES: While effective in reducing the risk of venous thromboembolism (VTE) following major orthopedic surgery (MOS), antithrombotics can increase the risk of major bleeding. We assessed impact of major bleeding following MOS on length of stay (LOS) and inpatient charges. METHODS: Using a database containing information on ~750,000 admissions annually to 100+ US acute-care hospitals (MQProfile, Cardinal Information Corp.), we identified all patients whom underwent MOS between January 1, 1998 and December 13, 2000. Patients were stratified according to whether or not they experienced major postoperative bleeding prior to hospital discharge, defined as: a) fatal bleeding; b) nonfatal bleeding at critical site; c) re-operation due to bleeding; and d) overt bleeding with bleeding index (BI)>2, where BI=number of blood units transfused plus pre-bleeding minus post-bleeding hemoglobin (g/dL) values. LOS and inpatient charges were compared between patients with and without major bleeding; findings were also examined for each of the constituent measures of the composite endpoint. RESULTS: A total of 23,518 patients were identified who underwent MOS; 2.6% experienced major bleeding (fatal bleeding, 0.1%; non-fatal bleeding at a critical site, 0.2%; re-operation due to bleeding, 0.7%; and overt bleeding associated with a BI>2, 1.7%). In multivariate analyses controlling for differences in baseline characteristics between patients with and without major bleeds, adjusted mean LOS was 1.8 days longer (95% CI: 1.5, 2.0) among the former (6.1 days vs. 4.3 days for those without bleeds); adjusted mean inpatient charges were $7,593 higher (95% CI: $6,622, $8,646) ($25,669 vs. $18,076). CONCLUSION: Major bleeding following MOS significantly increases LOS and hospital charges. Small absolute increases in the risk of major bleeding may translate into additional costs of inpatient care that counterbalance cost savings associated with VTE events averted. Cost of major bleeding following MOS should factor into choice of VTE prophylaxis.