PURPOSE: To evaluate therapeutic effects of a wearable medical device that provides continuous low-level topical heat therapy for wrist pain. METHODS AND MATERIALS: A randomized, multi-site, single (Investigator) blind, placebo-controlled, parallel design study. Ninety-four subjects, male or female, 18-65 years of age, with wrist pain, primarily due to strain or sprain (SS) or osteoarthritis (OA) of at least moderate or greater Pain Intensity were enrolled following informed consent. Of the 94, 24 had clinically diagnosed Carpal Tunnel Syndrome (CTS). Subjects were randomized to a heated wrist wrap (n=38; 40oC temperature, worn continuously for about 8 hours), an oral placebo treatment (n=40; 2 tablets q.i.d.), an active analgesic (acetaminophen, n=6; 500 mg/tablet X 2 tablets q.i.d.) treatment, or an unheated wrist wrap (n=6). The latter two groups were smaller sized, included only for blinding purposes. Treatment was on three consecutive days followed by two days of follow-up. Efficacy measurements included pain relief (0-5 scale), joint stiffness (NRS-101 scale), grip strength assessment (Jamar dynamometer), and patient-rated wrist evaluation (PRWE). CTS subjects also completed Symptom Severity and Functional Status Scales. Safety assessment was from evaluation of adverse events and skin assessments. ANALYSES: Pain Relief scores (Day 1-3, hour 0-8 mean) were analyzed using a generalized estimating equation (GEE) model to fit repeated measures data. A one tailed test was used to test for statistical evidence of greater 3-day pain relief in the heat wrap group compared to the placebo group. Analysis of covariance models (adjusted for baseline) were used to test for treatment differences between the Heat Wrap and Placebo groups for all other efficacy variables by time point. CTS and SS/OA groups were analyzed separately. RESULTS: HeatWrap therapy provided significant therapeutic benefits when compared to oral placebo for subjective pain relief (mean 1.68 vs. 1.15; p<0.05) and grip strength improvement (mean change in kg 6.4 vs. 2.5; p<0.05) in SS/OA population studied. Heat wrap therapy provided significant benefits compared to oral placebo in CTS group as evidenced by increased pain relief (mean 2.18 vs. 0.98; p<0.05), decreased joint stiffness (mean reduction 21.8 vs. 4.9; p<0.05), increased grip strength (mean change in kg 6.6 vs. -0.3; p<0.05), improvements on PRWE and CTS symptom severity and functional status scales. CONCLUSIONS: Continuous low-level topical heat therapy provided significant short-term therapeutic benefits in SS/OA subjects as well in CTS.