To investigate the impact of vaccines on sociodemographic characteristics, clinical profiles, and outcomes of SARS-CoV-2 infection among healthcare workers in South China during the period of Omicron variant dominance, a retrospective, analytical cross-sectional study was conducted. The findings revealed that while full vaccination could not prevent Omicron variant infection efficiently (26.51% uninfected vs 14.29% uninfected between vaccinated and unvaccinated participants, p = 0.506), it did substantially reduce the length of viral clearance significantly (p <
0.05), potentially facilitating quicker patient recovery. Unvaccination was found to be an independent risk factor for slow clearance when a linear regression analysis model was used (Coefficient: -3.516
95% CI: -6.425 to -0.607
p = 0.020). Therefore, all eligible individuals should be fully vaccinated to get prepared for a potential wave of epidemic in the future.