Study objective: During the delta surge of the COVID-19 pandemic in 2021, we sought to identify characteristics and beliefs associated with COVID-19 vaccination acceptance in parents of pediatric emergency department (ED) patients. Methods: We conducted a cross-sectional survey-based study of the parents of children aged 3 to 16 years presenting to 1 of 9 pediatric EDs from June to August 2021 to assess the parental acceptance of COVID-19 vaccines. Using multiple variable regression, we ascertained which factors were associated with parental and pediatric COVID-19 vaccination acceptance. Results: Of 1,491 parents approached, 1,298 (87%) participated, of whom 50% of the parents and 27% of their children aged 12 years or older and older were vaccinated. Characteristics associated with parental COVID-19 vaccination were trust in scientists (adjusted odds ratio [aOR] 5.11, 95% confidence interval [CI] 3.65 to 7.15), recent influenza vaccination (aOR 2.66, 95% CI 1.98 to 3.58), college degree (aOR 1.97, 95% CI 1.36 to 2.85), increasing parental age (aOR 1.80, 95% CI 1.45 to 2.22), a friend or family member hospitalized because of COVID-19 (aOR 1.34, 95% CI 1.05 to 1.72), and higher income (aOR 1.60, 95% CI 1.27 to 2.00). Characteristics associated with pediatric COVID-19 vaccination (children aged ≥12 years) or intended COVID-19 pediatric vaccination, once approved for use, (children aged <12 years) were parental trust in scientists (aOR 5.37, 95% CI 3.65 to 7.88), recent influenza vaccination (aOR 1.89, 95% CI 1.29 to 2.77), trust in the media (aOR 1.68, 95% CI 1.19 to 2.37), parental college degree (aOR 1.49, 95% CI 1.01 to 2.20), and increasing parental age (aOR 1.26, 95% CI 1.01 to 1.57). Conclusion: Overall COVID-19 vaccination acceptance was low. Trust in scientists had the strongest association with parental COVID-19 vaccine acceptance for both themselves and their children.