BackgroundPlant-based diets have gained attention due to their beneficial effects against major chronic diseases, though its association with multimorbidity is mostly unknow. ObjectiveWe examined the association between the healthful (hPDI) and unhealthful plant-based diet indices (uPDI) with multimorbidity among middle-aged and older adults from the U.S. MethodsData on 4,262 adults over 50 years was drawn from the 2012-2020 Health and Retirement Study (HRS) and 2013 Health Care and Nutrition Study (HCNS). Food consumption was collected at baseline with a food frequency questionnaire and two plant-based diet indices were derived: the hPDI, with positive scores for healthy plant foods and reverse scores for less healthy plant foods and animal foods; and the uPDI, with only positive scoring for less healthy plant foods. Complex multimorbidity, defined as ≥3 co-existent conditions, was ascertained with 8 self-reported conditions: hypertension, diabetes, cancer, chronic lung disease, heart disease, stroke, arthritis, and depression. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). ResultsAfter a median follow-up of 7.8 years, we documented 1,202 incident cases of multimorbidity. Compared with the lowest quartile, higher adherence to the hPDI was inversely associated with multimorbidity [HR (95% CI) for quartiles 3 and 4 were 0.77 (0.62–0.96) and 0.79 (0.63–0.98) respectively, p trend=0.02]. In addition, a 10-point increment in the hPDI was associated with a 11% lower incidence of multimorbidity (95% CI: 1%–20%). No significant associations were found for the uPDI after adjusting for sociodemographic and lifestyle factors. ConclusionsHigher adherence to the hPDI was inversely associated with multimorbidity among middle-age and older adults. Plant-based diets that emphasize consumption of high-quality plant foods may help prevent the development of complex multimorbidity.