question: BACKGROUND: There are some concerns about the effectiveness of the inactivated and vector-based vaccines against severe acute respiratory syndrome coronavirus 2 in real-world settings with the emergence of new mutations, especially variants of concern. Data derived from administrative repositories during mass vaccination campaigns or programs are of interest to study vaccine effectiveness. METHODS: Using 4-repository administrative data linkage, we conducted a historical cohort study on a target population of 1 882 148 inhabitants aged at least 18 years residing in southern Iran. RESULTS: We estimated a 71.9% [95% confidence interval [CI], 70.7%–73.1%], 81.5% [95% CI, 79.5%–83.4%], 67.5% [95% CI, 59.5%–75.6%], and 86.4% [95% CI, 84.1%–88.8%] hospital admission reduction for those who received the full vaccination schedule of BBIBP-CorV (Sinopharm), ChAdOx1-S/nCoV-19 vaccine (AZD1222, Oxford-AstraZeneca), rAd26-rAd5 (Gam-COVID-Vac, Sputnik V), and BIV1-CovIran (COVIran Barekat) vaccines, respectively. A high reduction in mortality (at least 85%) was observed in all age subgroups of the fully immunized population. CONCLUSIONS: The pragmatic implementation of a vaccination plan including all available vaccine options in the Iranian population was associated with a significant reduction in coronavirus disease 2019 (COVID-19) detected infections as well as hospital admissions and deaths associated with COVID-19.