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Objective. Sleep disturbance may limit improvement in pain outcomes if not directly addressed in treatment. Moreover, sleep problems may be exacerbated by opioid therapy. This study examined the effects of baseline sleep disturbance on improvement in pain outcomes using data from the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial, a pragmatic 12-month randomized trial of opioid vs nonopioid medication therapy. Design. Participants with chronic back pain or hip or knee osteoarthritis pain were randomized to either opioid therapy (N = 120) or nonopioid medication therapy (N = 120). Methods. We used mixed models for repeated measures to 1) test whether baseline sleep disturbance scores modified the effect of opioid vs nonopioid treatment on pain outcomes and 2) test baseline sleep disturbance scores as a predictor of less improvement in pain outcomes across both treatment groups. Results. The tests for interaction of sleep disturbance by treatment group were not significant. Higher sleep disturbance scores at baseline predicted less improvement in Brief Pain Inventory (BPI) interference (b = 0.058, P = 0.0002) and BPI severity (b = 0.026, P = 0.0164). Conclusions. Baseline sleep disturbance adversely affects pain response to treatment regardless of analgesic regimen. Recognition and treatment of sleep impairments that frequently co-occur with pain may optimize outcomes. [ABSTRACT FROM AUTHOR]