Overdose from illicit drugs is a leading cause of premature mortality in North America. Internationally, more than 65 supervised injecting facilities (SIFs), where drug users can inject pre-obtained illicit drugs, have been opened as part of various strategies to reduce the harms associated with drug use. We sought to determine whether the opening of an SIF in Vancouver, BC, Canada, was associated with a reduction in overdose mortality. We examined population-based overdose mortality rates for the period before (Jan 1, 2001, to Sept 20, 2003) and after (Sept 21, 2003, to Dec 31, 2005) the opening of the Vancouver SIF. The location of death was determined from provincial coroner records. We compared overdose fatality rates within an a priori specified 500 m radius of the SIF and for the rest of the city. Of 290 decedents, 229 (79·0%) were male, and the median age at death was 40 years (IQR 32-48 years). A third (89, 30·7%) of deaths occurred in city blocks within 500 m of the SIF. The fatal overdose rate in this area decreased by 35·0% after the opening of the SIF, from 253·8 to 165·1 deaths per 100,000 person-years (p=0·048). By contrast, during the same period, the fatal overdose rate in the rest of the city decreased by only 9·3%, from 7·6 to 6·9 deaths per 100,000 person-years (p=0·490). There was a significant interaction of rate differences across strata (p=0·049). SIFs should be considered where injection drug use is prevalent, particularly in areas with high densities of overdose. Vancouver Coastal Health, Canadian Institutes of Health Research, and the Michael Smith Foundation for Health Research. Copyright © 2011 Elsevier Ltd. All rights reserved.