Background Analyses of diagnostic performance of SARS-CoV-2 antigen rapid diagnostic tests (AG-RDTs) based on long-term data, population subgroups and many AG-RDT types are scarce. Aim We aimed to analyse sensitivity and specificity of AG-RDTs for subgroups based on age, incidence, sample type, reason for test, symptoms, vaccination status and the AG-RDT’s presence on approved lists. Methods We included AG-RDT results registered in Czechia’s Information System for Infectious Diseases between August and November 2021. Subpopulations were analysed based on 346,000 test results for which a confirmatory PCR test was recorded ≤ 3 days after the AG-RDT; 38 AG-RDTs with more than 100 PCR-positive and 300 PCR-negative samples were individually evaluated. Results Average sensitivity and specificity were 72.4% and 96.7%, respectively. We recorded lower sensitivity for age groups 0–12 (65.5%) and 13–18 years (65.3%). The sensitivity level rose with increasing SARS-CoV-2 incidence from 66.0% to 76.7%. Nasopharyngeal samples had the highest sensitivity and saliva the lowest. Sensitivity for preventive reasons was 63.6% vs 86.1% when testing for suspected infection. Sensitivity was 84.8% when one or more symptoms were reported compared with 57.1% for no symptoms. Vaccination was associated with a 4.2% higher sensitivity. Significantly higher sensitivity levels pertained to AG-RDTs on the World Health Organization Emergency Use List (WHO EUL), European Union Common List and the list of the United Kingdom’s Department of Health and Social Care. Conclusion AG-RDTs from approved lists should be considered, especially in situations associated with lower viral load. Results are limited to SARS-CoV-2 delta variant.