Low concentrations of serum anti-oxidants, including ascorbic acid and α-tocopherol, are associated with higher risks of many inflammatory diseases that interrelate with oral health. The present study examined the longitudinal relationship of serum ascorbic acid and α-tocopherol to periodontal disease in 224 Japanese individuals, aged 71 yrs, for whom data were available for the years 1999-2007. Participants were classified by tertiles of serum ascorbic acid and of α-tocopherol. Full-mouth periodontal status, measured as clinical attachment level (CAL), was recorded at baseline and annual follow-up examinations. The number of teeth with a loss of CAL ≥ 3 mm at any site over the study period was calculated as 'periodontal disease events'. Poisson regression analysis was conducted to assess predictors of periodontal disease events, with serum ascorbic acid and α-tocopherol as the primary predictors of interest. The multivariate adjusted relative risks (95% confidence intervals) in the highest, middle, and lowest tertiles were 1.00 (reference), 1.12 (1.01-1.26), and 1.30 (1.16-1.47) for ascorbic acid and 1.00 (reference), 1.09 (0.98-1.21), and 1.15 (1.04-1.28) for α-tocopherol, respectively. Our findings support the hypothesis that low serum levels of ascorbic acid and α-tocopherol may be a risk factor for periodontal disease in Japanese elderly.