Thirty-five inpatients at a Stockholm hospital drug user detoxification unit received single-session Motivational Interviewing (MI) between 2006 and 2008. At baseline and after 3 months, they were compared to a semi-randomized control group of 52 patients with treatment as usual. In the MI group, self-efficacy increased regarding abstention in connection with positive feelings, appreciation of positive drug effects increased, and participants tended to transition toward preparation/action stages of change. Despite implementation challenges, the study demonstrates the feasibility and effectiveness of single-session MI delivery in the inpatient drug detoxification setting and suggests paths for future research on delivery of single-session MI.