Evidence for the association of diet and gastric cancer is equivocal, and the majority of previous studies have not evaluated the interaction of diet and infection with Helicobacter pylori, the leading risk factor for gastric cancer. We examined these associations among 226 cases and 451 controls nested within a prospective cohort. Dietary intakes were calculated from validated food frequency questionnaires. Blood levels of 15 antibodies to Helicobacter pylori proteins were assessed using multiplex serology. Odds ratios (ORs) were calculated using logistic regression. Among individuals infected with high-risk Helicobacter pylori (sero-positivity to 5-6 virulent H. pylori proteins), increasing intake of red meat, heme iron, and sodium increased risk (comparing highest tertile to lowest: ORs [95% confidence interval {CI}]: 1.85 [1.01-3.40]; 1.95 [1.06-3.57]; and 1.76 [0.91-3.43], respectively) while increasing intake of fruit decreased gastric cancer risk (comparing highest tertile of intake to lowest: OR [95% CI]: 0.52 [0.28-0.94]). No associations of diet with risk were found among individuals infected with low-risk H. pylori (P for interaction for red meat and sodium: 0.02 and 0.01, respectively). In this population with over 90% prevalence of CagA-positive H. pylori infection, categorizing individuals using H. pylori multiplex serology may identify individuals for whom a diet intervention may be effective.