The Canadian national Health Technology Assessment (HTA) is the Canadian Agency for Drugs and Technologies in Health (CADTH) which evaluates the clinical and economic benefits of new therapies to make public reimbursement recommendations (except Quebec). In addition, the Patented Medicine Prices Review Board (PMPRB) has, since 1980, set a national ceiling price for new therapies based on their assessment of their relative therapeutic benefit, their international price and/or domestic therapeutic class price. In 2010, provincial governments established the pan-Canadian Pharmaceutical Alliance (pCPA) to collectively negotiate rebates off the list price for public plans. This research aims to evaluate which of these steps (PMPRB/CADTH/pCPA) is the most challenging for new therapies to overcome. All publicly-available CADTH, PMPRB and pCPA patented drug reports were identified and key data extracted (to 04-JAN-2020). 751 PMPRB outcomes were identified (from 01-JAN-2010), 85% were “within guidance”, 6.8% “does not trigger an investigation”, 2.8% “subject to investigation”, and only 4.8% subject to a “VCU” (Voluntary Compliance Undertaking). 379 completed CADTH appraisals were identified (from 01-JAN-2010), 3% were recommended with no restriction/conditions, 69% recommended with restrictions/conditions, and 28% not recommended. 526 pCPA negotiation outcomes were identified, 65% were concluded with agreement, 10% were concluded without agreement, in 15% negotiations were not pursued, and 10% were ongoing/under consideration. Currently, the substantial hurdles to clear for new therapies in Canada are the CADTH assessment and the pCPA negotiations based upon this assessment. To date, the PMPRB has rarely (<5% cases) issued VCUs to regulate drug prices. However, significant PMPRB reforms are due to be implemented from 01-JUL-2021, including changing the reference basket of countries and allowing their consideration of economic impact, which will significantly increase the number of drugs and magnitude of effect on drug prices.