Across Canada, there were notable differences in the rollout of provincial/territorial COVID-19 vaccination programs, reflecting diverse sociodemographic profiles, geopolitical landscapes, health system designs, and pandemic experiences. We collected information regarding underlying principles and goals, governance and authority, transparency and diversity of communications, activities to strengthen infrastructure and workforce capacity, and entitlement and access in four diverse provinces (British Columbia, Saskatchewan, Ontario, Nova Scotia). Through cross-case analysis, we observed significant differences in provincial rollouts of the primary two-dose vaccination series in adults between December 2020 and December 2021. Nova Scotia was the only province to state explicit coverage goals and adhere to plans tying coverage to the relaxation of public health measures. Both Nova Scotia and British Columbia implemented fully centralized vaccination booking systems. In contrast, Saskatchewan's initial highly centralized approach enabled the rapid delivery of first doses; however, rollout of second doses was slower and more decentralized, occurring primarily through community pharmacies. In alignment with its decentralized health system, Ontario pursued a regionalized approach, primarily led by its existing public health unit network. Our research suggests explicit goals, centralized booking, and flexible delivery strategies improved uptake; however, ongoing learning will be crucial for informing the success of future vaccination efforts.