Given once daily, extended-release (ER) tramadol HCl (ULTRAM^® ER) reduces pain and related symptoms of osteoarthritis (OA). Two 12-week, double-blind, placebo-controlled, randomized, parallel-group studies were conducted to compare the analgesic efficacy, safety, and tolerability of tramadol ER (100, 200, 300, and 400 mg for Study A and 100, 200, and 300 mg for Study B) as compared to placebo in patients (20-80 years) with moderate-to-severe pain due to radiographically-confirmed OA of the knee or hip (Study A, N = 1020; Study B, N = 1011). The effects of pain on sleep were evaluated using the Chronic Pain Sleep Inventory (CPSI) based on a 100-mm VAS (0 = never, 100 = always) for both studies. The overall quality of sleep was assessed using a 100-mm VAS (0 = very poor, 100 = excellent). The present post-hoc analysis evaluated tramadol ER 100, 200, and 300 mg in patients (n = 1608) from both studies using the CPSI scores to evaluate efficacy. Compared to placebo, all tramadol ER dose groups showed significant improvement in scores from baseline as early as Week 1 and were maintained through Week 12 for overall sleep quality (P ≤0.022). The tramadol ER 200- and 300-mg groups achieved significant improvement in scores from baseline at Week 1 through Week 12 and tramadol ER 100 mg showed significant improvement from baseline at Week 3 through Week 12 in being awakened by pain in the night and in the morning, and less trouble falling asleep due to pain compared to placebo (all, P ≤0.046). The most commonly reported adverse events in both studies were dizziness, nausea, constipation, somnolence, and pruritus. Therefore, as shown in these studies, improvements in analgesia were associated with a significant reduction in pain-related sleep problems in patients with OA.