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Objective: The aims of this study were to investigate occupational and non-work-related risk factors of coronavirus disease 2019 among health care workers (HCWs) in Vancouver Coastal Health, British Columbia, Canada, and to examine how HCWs described their experiences., Methods: This was a matched case-control study using data from online and phone questionnaires with optional open-ended questions completed by HCWs who sought severe acute respiratory syndrome coronavirus 2 testing between March 2020 and March 2021. Conditional logistic regression and thematic analysis were utilized., Results: Providing direct care to coronavirus disease 2019 patients during the intermediate cohort period (adjusted odds ratio, 1.90; 95% confidence interval, 1.04 to 3.46) and community exposure to a known case in the late cohort period (adjusted odds ratio, 3.595%; confidence interval, 1.86 to 6.83) were associated with higher infection odds. Suboptimal communication, mental stress, and situations perceived as unsafe were common sources of dissatisfaction., Conclusions: Varying levels of risk between occupational groups call for wider targeting of infection prevention measures. Strategies for mitigating community exposure and supporting HCW resilience are required., Competing Interests: Conflict of interest: A.I.O. and A.Y. earn fees for consultancy services to Vancouver Coastal Health. J.G. earns salaries from Vancouver Coastal Health. Vancouver Coastal Health played no role in the design and implementation of this project or in the writing of this manuscript. K.L., S.B., and A.I.O. have parts of their salary paid out of grants from the International Development Research Centre and the Canadian Institutes of Health Research. The other authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)