BACKGROUND: Before the SARS-CoV-2 Delta variant arrived in Vietnam, case rates suggested seroprevalence of SARS-CoV-2 was low. Beginning in March 2021, we assessed different dosing schedules and adverse events following immunization (AEFIs) for ChAdOx1 nCoV-19 vaccine among healthcare workers (HCWs). METHODS: We performed a prospective cohort study to estimate the prevalence of IgG antibodies to SARS-CoV-2 before and after ChAdOx1 nCoV-19 vaccination. We conducted antibody testing among HCWs in February 2021 (baseline), before the second dose (June-July 2021), and 1 and 3 months after the second dose. We detected antibodies to SARS-CoV-2 using Tetracore® FlexImmArray™, and surrogate neutralizing antibodies using GenScript cPass™. Neither assay can distinguish natural from vaccine-induced antibodies. We assessed AEFIs through interview post-dose 1 and 1 month post-dose 2. RESULTS: Before vaccination, 1/617 participants (0.16%) had antibodies to SARS-CoV-2. Of these 617, 405 were vaccinated with ChAdOx1 nCoV-19 with 4-8- (60%), 9-12- (27%), or ≥13-week (13%) intervals between the 2 doses. Three months following series completion, 99% and 97% of vaccinated participants had ≥1 sample with detectable antibodies and surrogate neutralizing antibodies against SARS-CoV-2, respectively. We observed no significant differences among those with different dosing intervals at last follow-up. All participants reported PCR testing for SARS-CoV-2 during the study; 2 (0.5%) were laboratory-confirmed. AEFIs were more frequent post-dose 1 (81%) vs post-dose 2 (21%). CONCLUSIONS: In this population, regardless of dosing interval, ChAdOx1 nCoV-19 induced antibodies within 3 months of the second dose. These findings may offer flexibility to policymakers when balancing programmatic considerations with vaccine effectiveness.