Estimated and potential medical costs of treating patients infected with human immunodeficiency virus (HIV) in urban areas of high HIV prevalence have not been well defined. We estimated the total medical cost of HIV disease among injection drug users in Vancouver, British Columbia, Canada, assuming stable and increasing HIV prevalence. Total medical costs were estimated by multiplying the average lifetime medical cost per person by the number of HIV-infected individuals. We assumed the cost of each HIV infection to be 150,000 Canadian dollars, based on empirical data, and HIV prevalence estimates were derived from the Vancouver Injection Drug Users Study (VIDUS) and external data sources. By use of Monte Carlo simulation methodology, we performed sensitivity analyses to estimate total medical cost, assuming the HIV prevalence remained stable at 31% and under a scenario in which the prevalence rose to 50%. Expected medical expenditures based on current HIV prevalence levels were estimated as 215,852,613 Canadian dollars. If prevalence rises to 50% as reported in other urban centers, the median estimated medical cost would be approximately 348,935,865 Canadian dollars. This represents a difference in the total costs between the two scenarios of 133,083,253 Canadian dollars. Health planners should consider that predicted medical expenditures related to the HIV epidemic among injection drug users in our setting may cost an estimated 215,852,613 Canadian dollars. If funding cannot be found for appropriate prevention interventions and the prevalence rises to 50%, a further 133,083,253 Canadian dollars may be required.