We aimed to examine rates of COVID-19 vaccination to elucidate the need for targeted public health interventions. We retrospectively reviewed the electronic medical files of all adults registered in a central district in Israel from 1 January 2021 to 31 March 2022. The population was characterized by vaccination status against COVID-19 and the number of doses received. Univariate and multivariable analyses were used to identify predictors of low vaccination rates that required targeted interventions. Of the 246,543 subjects included in the study, 207,911 (84.3%) were vaccinated. The minority groups of ultra-Orthodox Jews and Arabs had lower vaccination rates than the non-ultra-Orthodox Jews (68.7%, 80.5% and 87.7%, respectively, p < 0.001). Adults of low socioeconomic status (SES) had lower vaccination rates compared to those of high SES (74.4% vs. 90.8%, p < 0.001). Adults aged 20–59 years had a lower vaccination rate than those ≥60 years (80.0% vs. 92.1%, p < 0.0001). Multivariate analysis identified five independent variables that were significantly (p < 0.001) associated with low vaccination rates: minority groups of the ultra-Orthodox sector and Arab population, and underlying conditions of asthma, smoking and diabetes mellitus (odds ratios: 0.484, 0.453, 0.843, 0.901 and 0.929, respectively). Specific targeted public health interventions towards these subpopulations with significantly lower rates of vaccination are suggested.