Plant-based diets, often referred to as vegetarian diets, are associated with health benefits. However, the association with mortality is less clear. We investigated associations between plant-based diet indexes and all-cause and cardiovascular disease mortality in a nationally representative sample of US adults. Analyses were based on 11,879 participants (20–80 y of age) from NHANES III (1988–1994) linked to data on all-cause and cardiovascular disease mortality through 2011. We constructed an overall plant-based diet index (PDI), which assigns positive scores for plant foods and negative scores for animal foods, on the basis of a food-frequency questionnaire administered at baseline. We also constructed a healthful PDI (hPDI), in which only healthy plant foods received positive scores, and a less-healthful (unhealthy) PDI (uPDI), in which only less-healthful plant foods received positive scores. Cox proportional hazards models were used to estimate the association between plant–based diet consumption in 1988–1994 and subsequent mortality. We tested for effect modification by sex. In the overall sample, PDI and uPDI were not associated with all-cause or cardiovascular disease mortality after controlling for demographic characteristics, socioeconomic factors, and health behaviors. However, among those with an hPDI score above the median, a 10-unit increase in hPDI was associated with a 5% lower risk in all-cause mortality in the overall study population (HR: 0.95; 95% CI: 0.91, 0.98) and among women (HR: 0.94; 95% CI: 0.88, 0.99), but not among men (HR: 0.95; 95% CI: 0.90, 1.01). There was no effect modification by sex (P-interaction > 0.10). A nonlinear association between hPDI and all-cause mortality was observed. Healthy plant-based diet scores above the median were associated with a lower risk of all-cause mortality in US adults. Future research exploring the impact of quality of plant-based diets on long-term health outcomes is necessary.