Background Healthcare workers (HCWs) have suffered considerable morbidity and mortality during the COVID-19 pandemic. Few studies have evaluated Coronavac vaccine effectiveness (VE), particularly in eastern Europe, where the vaccine has been widely used. Methods We conducted a prospective cohort study among HCWs in seven hospitals in Baku, Azerbaijan between May 17 to December 1, 2021, to evaluate primary series (two-dose) CoronaVac VE against symptomatic SARS-CoV-2 infection. Participants completed weekly symptom questionnaires, provided nasal swabs for SARS-CoV-2 RT-PCR testing when symptomatic, and provided serology samples at enrolment that were tested for anti-spike and anti-nucleocapsid antibodies. We estimated VE as (1 – hazard ratio)*100 using a Cox proportional hazards model with vaccination status as a time-varying covariate. Results We enrolled 1582 HCWs. At enrolment, 1040 (66%) had received two doses of CoronaVac; 421 (27%) were unvaccinated. During the study period, 72 PCR-positive SARS-CoV-2 infections occurred; 36/39 (92%) sequenced samples were classified as delta variant. The adjusted primary series VE against COVID-19 illness was 29% (95% CI:-51%;67%). For the delta-predominant period, adjusted primary series VE was 19% (95% CI:-81%;64%). For the entire analysis period, adjusted primary series VE was 39% (95% CI:-40%;73%) for HCW vaccinated within 14–149 days, and 19% (95%CI:-81;63) for those vaccinated ≥150 days. Conclusions During a delta-predominant period in Azerbaijan, point estimates suggest that primary series CoronaVac protected nearly 1 in 3 HCWs against COVID-19, but this finding was not statistically significant. Our findings underscore the need to consider booster doses in individuals who have received primary series CoronaVac.