This case study refutes some controversial findings about a minor connection between the vaccination coverage and the spread of COVID-19. We try to eliminate some methodological shortcomings and risks, which are included in such previously published studies. Firstly, our selection comprises all regional units in one country. Secondly, the quality of data is basically identical in all examined regions within the country. Thirdly, all Slovak regions had an equal starting position. They were at the same stages of the COVID-19 wave, and the measures taken were analogous in all regions. Slovakia with a significantly different vaccination rates among regions is a very suitable study case. We used the empirical data at the level of its LAU 1 regions for the two latest COVID-19 waves at that time (Delta, Omicron). The methods of regression analysis and geostatistical methods were applied in the study. Indubitably, there is an obvious link between the vaccination coverage and the spread of COVID-19. We have shown that the incidence-trajectories among regions vary based on the vaccination rates. The positivity and incidence in the most vaccinated regional populations were significantly lower than in the least vaccinated regions in a whole analyzed period. Their values in the best vaccinated regions were lower by roughly 20–25 % during the delta and omicron wave-peaks. Using the spatial autocorrelation, we also managed to clearly identify a close relationship between vaccination on the one hand and standardized incidence and positivity on the other hand, although some regions deviated from this general finding.