OBJECTIVE: The COVID-19 pandemic is associated with increased difficulties in emotional well-being among healthcare workers. The current investigation assesses how changes in depression and anxiety symptoms fluctuate relative to resilience across three time points: baseline, 1-year, and 2-year follow-up among a cohort of physicians and nurses ( n = 728). METHODS: Generalized linear mixed modeling for repeated-measures was used to assess the association between resilience and mental health symptoms using validated measures for all variables. RESULTS: The odds of probable anxiety were reduced by 81% for each one-unit increase in resilience (odds ratio = 0.19, 95% confidence interval [0.14, 0.26]). The odds of probable depression were reduced by 88% for each one-unit increase in BRS (odds ratio = 0.12, 95% confidence interval [0.07, 0.2]). CONCLUSIONS: Results highlight the importance of developing and implementing interventions that foster resilience among healthcare workers.