Methadone maintenance treatment (MMT) has important protective effects related to reduced illicit opioid use, infectious disease transmission, and overdose mortality. Adherence to MMT has not been examined among homeless people. We measured MMT adherence and reported relevant characteristics among homeless adults experiencing mental illness in Vancouver, British Columbia, Canada. The level of adherence to MMT was very low among homeless adults experiencing mental illness. Efforts are needed to improve adherence to MMT as a means of reducing illicit substance use, preventing overdose deaths, and attenuating infectious disease transmission.