OBJECTIVES: To evaluate the efficacy and safety of adding tramadol 37.5 mg/acetaminophen (APAP) 325 mg combination tablets (tramadol/APAP) to existing therapy for painful osteoarthritis (OA) flare in a subset of elderly patients. DESIGN: Randomized, double-blind, placebo-controlled, 10-day add-on study. SETTING: Thirty outpatient centers. PARTICIPANTS: Of 308 patients with painful OA flare, a subset of 113 patients aged 65 and older. MEASUREMENTS: Average daily pain intensity and pain relief scores for Days 1 through 5 and secondary quality-of-life measures and medication assessments. METHODS: Patients received one or two tramadol/APAP tablets or placebo four times per day for 10 days during ongoing nonselective or cyclooxygenase (COX)-2-selective nonsteroidal antiinflammatory drug (NSAID) therapy. RESULTS: Tramadol/APAP (n=69) was significantly superior to placebo (n=44) for average daily pain intensity (P=.034) and pain relief (P=.010) for Days 1 through 5 and Days 1 through 10 (P=.012 and P=.019, respectively). Tramadol/APAP had significantly better investigator (P<.001) and patient (P=.001) overall medication assessments and significantly better scores on three of four Western Ontario and McMaster Universities Osteoarthritis Index measures (P< or =.027). Most common adverse events with tramadol/APAP were nausea (18.8%), vomiting (13.0%), dizziness (11.6%), and constipation (4.3%), with an incidence similar to that of the overall study population. Mean daily dose of tramadol/APAP was 4.5 tablets (168 mg/1,458 mg). CONCLUSION: Tramadol/APAP add-on therapy effectively managed painful OA flare in this elderly subset and was generally well tolerated.