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Aim We tested the efficacy of a brief intervention based on motivational interviewing (MI) to reduce high-risk injection behaviours over a 6-month period among people who inject drugs (PWID). Design A single-site two-group parallel randomized controlled trial comparing MI with a brief educational intervention (EI). Setting A study office located in downtown Montréal, Canada, close to the community-based harm reduction programmes where PWID were recruited. Participants PWID who had shared drug injection equipment or shared drugs by backloading or frontloading in the month prior to recruitment were randomized to either the MI (112) or EI (109) groups. Intervention The MI aimed to (1) encourage PWID to voice their desires, needs and reasons to change behaviours; (2) boost motivation to change behaviours; and (3) when the person was ready, support the plan he or she chose to reduce injection risk behaviours. The EI consisted of an individual session about safe injection behaviours. Measurements The primary outcome was defined as having any of these risk behaviours at 6 months: having shared syringes, containers, filters or water to inject drugs in the previous month and backloading/frontloading; each behaviour was examined separately, as secondary outcomes. Findings The probability of reporting a risk injection behaviour decreased in both the MI and the EI groups. At 6-month follow-up, participants who reported any risk behaviours were 50% [odds ratio (OR) = 0.50; confidence interval (CI) = 0.13-0.87] less likely to be in the MI group than in the EI group as well as those who reported sharing containers (OR = 0.50; CI = 0.09-0.90). PWID who reported sharing equipment excluding syringes were 53% less likely to be in the MI group (OR = 0.47; CI = 0.11-0.84). Conclusions A brief motivational interviewing intervention was more effective than a brief educational intervention in reducing some high risk injecting behaviours up in the subsequent 6 months. [ABSTRACT FROM AUTHOR]