OBJECTIVES: To evaluate the efficacy and safety of the centrally acting analgesic, tapentadol ER, for the management of moderate to severe osteoarthritis knee pain; health status was evaluated using the EuroQol-5 Dimension (EQ-5D) questionnaire. METHODS: Patients received twice-daily doses of tapentadol ER (100-250mg), oxycodone HCl controlled release (CR; 20-50mg), or placebo over a 15-week treatment period.  Patients completed the EQ-5D (evaluates mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) at baseline and at prespecified time points. RESULTS: Efficacy and safety were evaluated for 1,023 patients who received ≥1 dose of study medication.  Overall, the change from baseline in the EQ-5D health status index was significantly greater with tapentadol ER versus both oxycodone CR and placebo (least squares mean difference [95% confidence interval] between tapentadol ER and oxycodone CR, 0.07 [0.03,0.10; P<0.001]; between tapentadol ER and placebo, 0.05 [0.02,0.09; P=0.004]).  Differences between oxycodone CR and placebo were not significant (−0.01 [−0.05,0.02; P=0.449]).  Across all treatment groups at baseline, the percentages of patients reporting no problems in each of the EQ-5D dimensions were as follows: mobility, 9%-10%; self-care, 77%-82%; usual activities, 14%-17%; pain/discomfort, 0%-1%; and anxiety/depression, 68%-70%.  At endpoint, the percentages of patients reporting no problems were mobility: placebo, 16.3%; tapentadol ER, 25.0%; oxycodone CR, 16.7%; self-care: placebo, 75.1%; tapentadol ER, 81.1%; oxycodone CR, 80.1%; usual activities: placebo, 26.1%; tapentadol ER, 33.7%; oxycodone CR, 27.2%; pain/discomfort: placebo, 5.6%; tapentadol ER, 9.0%; oxycodone CR 4.7%; and anxiety/depression: placebo, 71.8%; tapentadol ER, 70.9%; oxycodone CR, 69.6%.  A total of 61.1%, 75.9%, and 87.4% of patients who received placebo, tapentadol ER, and oxycodone CR, respectively, reported ≥1 treatment-emergent adverse event. CONCLUSIONS: Treatment with tapentadol ER (100-250mg bid) significantly improved overall health status compared with placebo and oxycodone HCl CR (20-50mg bid) in patients with moderate to severe chronic osteoarthritis knee pain.