To evaluate methylnaltrexone for opioid-induced constipation in patients with and without cancer. This post hoc analysis comprises two Phase III, multicenter, double-blind, randomized studies of advanced-illness patients who received methylnaltrexone subcutaneous injection or placebo. Significantly more patients treated with methylnaltrexone than placebo experienced laxation within 4 (cancer = 55.5 vs 15.5%; noncancer = 55.6 vs 12.8%) and 24 (cancer = 64.7 vs 29.8%; noncancer = 64.4 vs 30.8%) h after the first dose (p < 0.01 vs placebo). Regardless of cancer status, methylnaltrexone reduced median time to laxation and improved constipation relief without impacting opioid analgesia or withdrawal symptoms. Methylnaltrexone provided significant improvements in opioid-induced constipation over placebo in advanced-illness patients with and without cancer. Study 301: NCT00401362; Study 302: NCT00402038.