Assessing vaccine efficacy (VE) during emerging epidemics is challenging due to unpredictable disease transmission dynamics. We aimed to investigate the impact of vaccine randomized controlled trials (RCTs) timing on estimates of VE and sample sizes during future epidemics of emerging respiratory diseases. We developed an age-structured susceptible-exposed-infected-asymptomatically infected-removed (SEIAR) compartment models using 2022 Korean population, and COVID-19 and 2009 A/H1N1 pandemic influenza parameters. Various RCT scenarios were tested to calculate VE estimates, sample size and power by varying RCT timings (using the epidemic peak as the base,