OBJECTIVES: To assess the effect of subcutaneous Methylnaltrexone on patient reported constipation specific quality of life. METHODS: In a double blind study 469 subjects on opioid therapy for chronic non-malignant pain and opioid-induced constipation were randomized to either methylnaltrexone QD or QOD dosing or placebo for 4 weeks and 460 received at least 1 dose. Subjects were eligible if they had an opioid dose of ≥50 mg oral morphine equivalents/day for ≥2 weeks and < 3 rescue free bowel movements (RFBMs)/week. Patients reported constipation specific quality of life using the Patient Assessment of Constipation – Quality of Life (PAC-QOL) questionnaire which is a validated 28 –item questionnaire assessing physical discomfort (4 items), psychosocial discomfort (8 items), worries and concerns (11 items) and treatment satisfaction (5 items) on a 5-point Likert scale. Higher scores indicate poorer QOL. Change from baseline in mean domain and total scores were compared between methylnaltrexone and placebo arms on day 28 using analysis of covariance, with treatment group as factor and baseline score as covariate. RESULTS: Majority of the patients in the study were female (60%), Caucasian (90%), average age was 49 years and reported back pain (60%). At the end of the double blind period (day 28), a significantly greater improvement was detected in the methylnaltrexone QD dosing group compared to placebo for: physical discomfort (-0.81 vs. –0.39;p<0.001), psychosocial discomfort (-0.51 vs. –0.32; p<0.05), worries and concerns (-0.69 vs. –0.38; p<0.001), satisfaction (-0.96 vs.-0.48; p<0.001) and overall PAC-QOL score (-0.74 vs. –0.39; p<0.001). Significantly greater improvement in physical discomfort (-0.60 vs. –0.39; p<0.05), satisfaction (-0.79 vs. –0.48; p<0.05) and the overall PAC-QOL scores (-0.59 vs. –0.39; p<0.05) were found in the methylnaltrexone QOD dosing group compared to placebo. CONCLUSIONS: Subcutaneous methylnaltrexone showed a significantly greater improvement in patient reported constipation specific quality of life compared to placebo.