Purpose: We previously proposed an oxidative balance score (OBS) that combines pro- and anti-oxidant exposures to represent the overall oxidative balance status of an individual. In this study, we investigated associations of the OBS with all-cause and cause-specific mortality, and explored alternative OBS weighting methods in the Reasons for Geographic and Racial Differences in Stroke Study cohort. Methods: The OBS was calculated by combining information from 14 a priori selected pro- and anti-oxidant factors and then divided into quartiles with the lowest quartile (predominance of pro-oxidants) as reference. Cox proportional hazard models were used to estimate adjusted hazard ratios and 95% confidence intervals for each OBS category compared with the reference. Results: Over a median 5.8years of follow-up, 2079 of the 21,031 participants died. The multivariable-adjusted hazard ratios (95% confidence interval) for all-cause, cancer, and noncancer mortality for those in the highest versus the lowest equal-weighting OBS quartile were 0.70 (0.61-0.81), 0.50 (0.37-0.67), and 0.77 (0.66-0.89), respectively (P trend<.01 for all). Similar results were observed with all weighting methods. Conclusions: These results suggest that individuals with a greater balance of antioxidant to pro-oxidant lifestyle exposures may have lower mortality.