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This retrospective multicenter cohort study assessed temporal changes in the severity and mortality rate of blastomycosis in Quebec, Canada, and identified risk factors for death in patients with blastomycosis in 1988–2016. The primary outcome was 90-day all-cause deaths. Among 185 patients, 122 (66%) needed hospitalization and 30 (16%) died. We noted increases in the proportion of severe cases, in age at diagnosis and in the proportion of diabetic and immunocompromised patients over time. Independent risk factors for death were age (adjusted odds ratio [aOR] 1.04, 95% CI 1.00–1.07), immunosuppression (aOR 4.2, 95% CI 1.5–11.6), and involvement of >2 lung lobes (aOR 5.3, 95% CI 1.9–14.3). There was no association between the Blastomyces genotype group and all-cause mortality. The proportion of severe cases of blastomycosis has increased in Quebec over the past 30 years, partially explained by the higher number of immunosuppressed patients.