Changing patterns of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) incidence worldwide suggest distinct etiologies. Although associations between fruit and vegetable intake and both ESCC and EAC have been found in multiple ecological and case-control studies, few prospective studies have investigated these associations. We prospectively examined these associations in 490,802 participants of the National Institutes of Health (NIH)-AARP Diet and Health Study using Cox models adjusted for age, alcohol intake, body mass index, cigarette smoking, education, physical activity and total energy intake. We present hazard ratios and 95% confidence intervals per serving per 1,000 calories. During 2,193,751 person years of follow-up, 103 participants were diagnosed with ESCC and 213 participants with EAC. We found a significant inverse association between total fruit and vegetable intake and ESCC risk (HR: 0.78, 95% CI: 0.67-0.91), but not EAC risk (0.98, 0.90-1.08). In models mutually adjusted for fruit and vegetable intake, the protective association with ESCC was stronger for fruits (0.73, 0.57-0.93) than for vegetables (0.84, 0.66-1.07). When we examined botanical subgroups, we observed significant protective associations for ESCC and intake of Rosacea (apples, peaches, nectarines, plums, pears and strawberries) and Rutaceae (citrus fruits). A significant inverse association between EAC and Chenopodiaceae (spinach) intake was observed. Results from our study suggest that the relation of fruit and vegetable intake and esophageal cancer risk may vary by histologic type.