Objectives: The aim of the study was to reappraise the precise costs of HIV care and cost drivers, to determine the optimal tools for modelling costs for HIV care, and to understand the implications of changing medical management of HIV‐infected patients for both subsequent outcomes and health care budgets. Methods: We obtained all drug, laboratory, out‐patient and in‐patient care costs for all HIV‐infected patients followed between 1 January 2006 and 31 December 2017 (2017 Cdn$). Mean cost per patient per month (PPPM) was used as the standard comparator value. Patients were stratified based on CD4 count: (1) ≤ 75, (2) 76–200, (3) 201–500 and (4) > 500 cells/μL. We determined the cost for only HIV‐related expenses. We compared current costs with costs previously reported for the same population. Results: The number of HIV‐infected patients in care doubled from 2006 to 2017; total costs increased from $12.4 to $30.1 million, with antiretroviral (ARV) drugs accounting for 78.8% of costs by 2017. Out‐patient/laboratory costs declined from 12% to 8.5%, while in‐patient costs exhibited more annual variation. Mean PPPM costs increased from $1316 in 2006 to $1712 in 2014, declining to $1446 in 2017. Higher PPPM costs were associated with CD4 counts < 200 cells/μL. Costs have shifted. While the cost of ARV drugs increased by 32%, the costs of out‐patient and in‐patient services decreased by 80% and 71%, respectively. Most of the decrease for in‐patient costs was attributable to a substantial decrease in HIV‐related hospitalizations. Conclusions: Although antiretroviral therapy (ART) provides immense benefits, it is not inexpensive. ARV drugs remain the largest cost driver. Hospital costs have remained low. Substantial costs of lifelong ART necessitate innovative, locally applicable strategies for ARV selection and use. [ABSTRACT FROM AUTHOR]