The study was conducted to estimate the protective effectiveness (PE) of complete primary or booster dose regimens of COVID-19 vaccines deployed in Bangladesh. The study was conducted in four hospitals in Dhaka between December 30, 2021, and August 31, 2022 following a test-negative design. Patients aged ≥18 years attended with COVID-like symptoms were enrolled and tested for RT-PCR. Test-negative controls were matched to confirmed cases at a 1:1 ratio considering site, date, and age groups. Conditional logistic regression was used to estimate the PE considering the association between receipt of complete primary with or without a booster regimen and development of COVID-19 disease symptoms. Whole genome sequencing (WGS) was carried out to confirm the variants. RT-PCR positive 847 cases were matched to 847 controls. WGS of strains revealed 6% to be the Delta variant and 94% was Omicron variant. The PE conferred by receipt of complete primary regimen with or without booster dose of any vaccine revealed no significant protection (15%, 95% CI: -11 to 36,  = .23) against any COVID-19 disease or severe disease (14%, 95%CI: -23 to 39,  = .42). However, there was a protective association between receipt of complete primary regimen with or without booster dose of one mRNA vaccine (Pfizer-BioNTech) against any COVID-19 disease (88% (95% CI: 26 to 98,  = .023)) for the first 90 days. The analysis suggested little vaccine effectiveness during Omicron surge, with the possible exception of one mRNA-vaccine 90 days after dosing.