ImportanceThe impact of adult-use cannabis legalization and subsequent commercialization (ie, increasing store and product access) on hospitalizations in Canada is unclear.ObjectivesTo examine changes in overall and subtypes of hospitalizations due to cannabis and associated factors following legalization in Canada and to compare changes between provinces.Design, Setting, and ParticipantsThis repeated cross-sectional analysis included all acute hospitalizations for individuals aged 15 to 105 years in Canada’s 4 most populous provinces (Ontario, Quebec, Alberta and British Columbia, population 26.9 million individuals in 2018). Data were obtained from routinely collected health administrative databases. Immediate and gradual changes in the age- and sex-standardized rates of hospitalizations due to cannabis were compared using an interrupted time series design over 3 time periods: prelegalization (January 2015 to September 2018), legalization with product and store restrictions (October 2018 to February 2020), and commercialization, which overlapped with the COVID-19 pandemic (March 2020 to March 2021).Main Outcomes and MeasuresRates of hospitalizations due to cannabis per 100 000 individuals and per 1000 all-cause hospital admissions.ResultsThere were 105 203 hospitalizations due to cannabis over the 7-year study period, 69 192 of which (65.8%) were among male individuals, and 34 678 (33%) of which were among individuals aged 15 to 24 years. Overall, the age- and sex-standardized rate of hospitalizations increased 1.62 times between January 2015 (3.99 per 100 000 individuals) and March 2021 (6.46 per 100 000 individuals). The largest relative increase in hospitalizations was for cannabis-induced psychosis (rate ratio, 1.40; 95% CI, 1.34 to 1.47 during the commercialization period relative to the prelegalization period). Nationally, legalization with restrictions was associated with a gradual monthly decrease of −0.06 (95% CI −0.08 to −0.03) in hospitalizations due to cannabis per 100 000 individuals. Commercialization and the COVID-19 pandemic were associated with an immediate increase of 0.83 (95% CI, 0.30 to 1.30) hospitalizations due to cannabis per 100 000 individuals. There was provincial variation in changes, with provinces with less mature legal markets experiencing the greatest declines immediately following legalization.Conclusions and RelevanceThis cross-sectional study found that legalization with restrictions was not associated with an increase in hospitalizations due to cannabis but commercialization was. The findings suggest that commercialization of cannabis may be associated with increases in cannabis-related health harms, including cannabis-induced psychosis.