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Objectives: Lengthy emergency department (ED) wait times caused by hospital access block is a growing concern for the Canadian health care system. Our objective was to quantify the impact of alternate-level-of-care on hospital access block and evaluate the likely effects of multiple interventions on ED wait times., Methods: Discrete-event simulation models were developed to simulate patient flows in EDs and acute care of six Canadian hospitals. The model was populated with administrative data from multiple sources (April 2017-March 2018). We simulated and assessed six different intervention scenarios' impact on three outcome measures: (1) time waiting for physician initial assessment, (2) time waiting for inpatient bed, and (3) patients who leave without being seen. We compared each scenario's outcome measures to the baseline scenario for each ED., Results: Eliminating 30% of medical inpatients' alternate-level-of-care days reduced the mean time waiting for inpatient bed by 0.25 to 4.22 h. Increasing ED physician coverage reduced the mean time waiting for physician initial assessment (∆ 0.16-0.46 h). High-quality care transitions targeting medical patients lowered the mean time waiting for inpatient bed for all EDs (∆ 0.34-6.85 h). Reducing ED visits for family practice sensitive conditions or improving continuity of care resulted in clinically negligible reductions in wait times and patients who leave without being seen rates., Conclusions: A moderate reduction in alternate-level-of-care hospital days for medical patients could alleviate access block and reduce ED wait times, although the magnitude of reduction varies by site. Increasing ED physician staffing and aligning physician capacity with inflow demand could also decrease wait time. Operational strategies for reducing ED wait times should prioritize resolving output and throughput factors rather than input factors., (© 2023. The Author(s), under exclusive licence to Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)