Background: Hepatitis B virus infection is a global health priority, and health-care personnel (HCP) have 10 times higher prevalence than the general population. Seromonitoring identifies those with low titers and vaccine nonresponders with increased risk. Objective: The objective of the study was to assess hepatitis B surface antibody (anti-HBs) titers and associated factors among HCP vaccinated against hepatitis B in a teaching hospital in Kerala. Methods: A cross-sectional study was done among 454 vaccinated HCP, and anti-HBs antibody titers were assessed by enzyme-linked immunosorbent assay method. Results: Participants included 162 (35.7%) doctors, 132 (29.3%) nursing and laboratory personnel, and 160 (35.3%) supporting staff. The mean age was 38.06 ± 11.33 years, and 72% were female. Majority (92.5%, 420) were seroprotected and 78.9% (358) with high (>100 mIU) titers. Moderate (10–100 mIU) and low (<10 mIU) level seroprotection was seen in 13.7% (62) and 7.5% (34), respectively. Incomplete vaccination, >10 years since vaccination, and age >40 years were independent predictors for poor seroprotection, while increasing doses and boosters were positively associated. Conclusions: Majority of vaccinated HCP were seroprotected. Incomplete schedules, older age, and prolonged time since vaccination can lead to decline in titers, and periodical seromonitoring should guide hepatitis B revaccination strategies.