HELPcB (Health Effects in High-Level Exposure to Polychlorinated Biphenyls [PCB]) is a surveillance program for former PCB-exposed workers of a capacitor recycling company and other concerned individuals. The aim of this study was to examine the influence of polychlorinated biphenyls (PCB) on the health-related quality of life (HRQL) and on quality-adjusted life years (QALY). The EQ-5D-3L questionnaire was used to determine the HRQL. After three cross-sectional examinations at intervals of 1 yr, the longitudinal development of QALY was compared by repeated-measurement analysis of covariance (ANCOVA). The cohort was split at the 95th percentile of the comparison group for each PCB congener; known confounders such as age were taken into account. A significant difference in height and development of QALY over time was shown for the higher chlorinated non-dioxin-like PCB (hcPCB) congeners. A significant between-groups effect was found on PCB 153, PCB 180, and the sum of hcPCB. It was found that QALY decreased in the high-burden group and QALY stabilized after yr 2 in the normal-burden group. Taking the dimensions of the EQ-5D into account, the between-groups effect seems to be based predominantly on the dimension anxiety. The development of the within-group effect, however, seems to be based on the dimension mobility. This study detected a significant influence of hcPCB on the development of HRQL and QALYs over time according to the level of internal PCB burden.