Introduction: Given once daily, tramadol HCl extended-release (ER; ULTRAM^® ER) reduces pain and related symptoms of osteoarthritis (OA). Methods: Two 12-week, double-blind, placebo-controlled, randomized, parallel-group studies were conducted to evaluate the analgesic efficacy, safety, and tolerability of tramadol ER (at least 200 mg for Study A and 100, 200, 300, or 400 mg for Study B) compared to placebo in patients (18-74 years) with moderate-to-severe pain due to radiographically-confirmed OA of the knee (Study A, N = 246, dose-titration) and knee or hip (Study B, N = 1,020, dose-ranging). The effects of pain on sleep were evaluated using the Chronic Pain Sleep Inventory (CPSI) based on a 100-mm visual analogue scale (VAS; 0 = never, 100 = always). The overall quality of sleep was assessed using a 100-mm VAS (0 = very poor, 100 = excellent). A Sleep Problems Index (SPI; composed of CPSI 1, CPSI 3, and CPSI 4) was used as a valid and reliable measure of sleep problems. This analysis evaluated the efficacy of tramadol ER in reducing sleep problems, as measured by the SPI, among patients with chronic OA pain using post-hoc analyses of data from patients in both studies. Results: Both studies showed a significant improvement in SPI scores from baseline to endpoint (Study A, tramadol ER vs placebo, P <0.05; Study B, tramadol ER 100, 200, and 300 mg vs placebo, all P <0.05). One study (Study B) showed significant improvements as early as Week 1 (P <0.05 for all doses). Once sleep improvements occurred in either study, they were maintained for the duration of the study. The most commonly reported adverse events for both studies were dizziness, nausea, constipation, headache, somnolence, and pruritus. Conclusion: One possible benefit of treating OA pain with tramadol ER is a significant reduction in sleep-related problems.