ObjectivePolychlorinated biphenyls (PCBs) have been reported to be a risk factor for premature death, while a high diet quality is thought to lower mortality risk. We aimed to examine whether PCBs were associated with higher all-cause and cause-specific mortality risk and whether such associations could be modified by the diet quality among US middle-aged and older adults. MethodsIncluded were 1259 participants aged 40 years or older from the 1999–2004 National Health and Nutrition Examination surveys. Exposure to PCBs was assessed in non-fasting serum samples, and mortality status was ascertained through December 31, 2019 using the public-use, linked mortality files. Diet quality was assessed using the Healthy Eating Index-2015 based on 24-h dietary recalls. Cox proportional hazard regression was applied to assess the associations of different PCB congener groups with mortality and the modifying effect by the diet quality. ResultsDuring a median follow-up of 17.75 years, 419 deaths occurred, including 131 from cardiovascular disease (CVD) and 102 from cancer. Serum concentrations of dioxin-like PCBs and non-dioxin-like PCBs were significantly associated with all-cause mortality, with hazard ratios (HRs) of 1.84 (95% confidence interval [CI], 1.10, 2.99) and 1.82 (1.09, 3.03) for extreme-tertile comparisons. A significant interaction was noted between dioxin-like PCBs and diet quality (P for interaction: 0.012), with a substantially more pronounced association among participants with a low diet quality (HR, 3.47; 95% CI: 1.29, 9.32), compared to those with a high diet quality (HR, 0.98; 95% CI: 0.40, 2.43). A similar weaker association was observed for total PCBs in participants with a high diet quality (P for interaction: 0.032). However, effect modifications by diet quality were not noted for the associations between different PCB groups and CVD mortality. ConclusionsWhile our findings need to be validated in other populations and mechanistic studies, they may suggest that a high quality diet could potentially attenuate the harmful effects of chronic PCB exposure.