Background: Research predicting the public health and fiscal impact of Supervised Injection Facilities (SIFs), across different cities in Canada, has reported positive results on the reduction of HIV cases among People Who Inject Drugs (PWID). Most of the existing studies have focused on the outcomes of Insite, located in the Vancouver Downtown Eastside (DTES). Previous attention has not been afforded to other affected areas of Canada. The current study seeks to address this deficiency by assessing the cost-effectiveness of opening a SIF in Saskatoon, Saskatchewan. Methods: We used two different mathematical models commonly used in the literature, including sensitivity analyses, to estimate the number of HIV infections averted due to the establishment of a SIF in the city of Saskatoon, Saskatchewan. Results: Based on cumulative cost-effectiveness results, SIF establishment is cost-effective. The benefit to cost ratio was conservatively estimated to be 1.35 for the first two potential facilities. The study relied on 34% and 14% needle sharing rates for sensitivity analyses. The result for both sensitivity analyses and the base line estimates indicated positive prospects for the establishment of a SIF in Saskatoon. Conclusion:The opening of a SIF in Saskatoon, Saskatchewan is financially prudent in the reduction of tax payers' expenses and averting HIV infection rates among PWID. Keywords: People Who Inject Drugs (PWID), HIV, Cost-Benefit Analysis, Canada Copyright: © 2015 by Kerman University of Medical Sciences Citation: Jozaghi E, Jackson A. Examining the potential role of a supervised injection facility in Saskatoon, Saskatchewan, to avert HIV among people who inject drugs.