**Background:** Plant-based diets (PBDs) are increasingly popular for their potential health benefits and environmental sustainability. However, previous research suggests that not all PBDs are equally beneficial — the composition and quality of plant foods may be critical. This study aimed to evaluate whether adherence to a healthful vs unhealthful type of PBD was associated with total and cause-specific mortality and with major chronic diseases (CVD, cancer, and fracture) in a large UK population, addressing potential adverse effects such as fracture risk that have been linked to strict vegan/vegetarian diets.
**Methods:** The study included up to 126,394 participants from the UK Biobank (aged 40-69 at recruitment, 2006-2010) who had completed at least two 24-hour dietary assessments using the Oxford WebQ tool. A healthful plant-based diet index (hPDI) and unhealthful plant-based diet index (uPDI) were constructed from 17 food groups. For hPDI, healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, tea/coffee) were scored positively, while less healthy plant foods (refined grains, potatoes, sugary drinks, fruit juices, sweets/desserts) and animal-derived foods were scored negatively; uPDI was scored oppositely. Scores were categorized into sex-specific quartiles. Cox proportional hazards regression models with age as the underlying time variable estimated hazard ratios (HRs) and 95% CIs, adjusted for sex, BMI, race/ethnicity, physical activity, smoking, alcohol, education, energy intake, polypharmacy, multimorbidity, aspirin use, and stratified by region. Additional adjustments included polygenic risk scores for CVD outcomes, menopausal status/hormone therapy for cancer, and vitamin/mineral supplement use for fracture. Follow-up ranged from 10.6 to 12.2 years across outcomes.
**Key Results:** During follow-up, there were 5,627 deaths (698 CVD, 3,275 cancer), 6,890 incident CVD cases (3,253 myocardial infarction, 1,151 ischemic stroke, 469 hemorrhagic stroke), 8,939 incident cancers (1,083 postmenopausal breast, 2,137 prostate, 959 colorectal), and 4,751 incident fractures (736 hip, 319 vertebrae). Compared with the lowest quartile, participants in the highest hPDI quartile had a 16% lower risk of all-cause mortality (HR 0.84; 95% CI 0.78-0.91; corrected P=0.004), a 7% lower risk of any cancer (HR 0.93; 95% CI 0.88-0.99; corrected P=0.03), and an 8% lower risk of total CVD (HR 0.92; 95% CI 0.86-0.99; corrected P=0.007). Specific CVD outcomes showed lower risks for myocardial infarction (HR 0.86; 95% CI 0.78-0.95; corrected P=0.004) and ischemic stroke (HR 0.84; 95% CI 0.71-0.99; corrected P=0.08). Conversely, higher uPDI scores were associated with a 23% higher risk of all-cause mortality (HR 1.23; 95% CI 1.14-1.32; corrected P=0.004), a 10% higher risk of any cancer (HR 1.10; 95% CI 1.03-1.17; corrected P=0.004), and a 21% higher risk of total CVD (HR 1.21; 95% CI 1.05-1.20; corrected P=0.004). No significant associations were found between either hPDI or uPDI and fracture risk or hemorrhagic stroke. Inverse associations between hPDI and CVD outcomes were independent of genetic disease risk (polygenic risk score tertiles). Subgroup analyses showed little heterogeneity, though the inverse association between hPDI and CVD mortality was observed among ever smokers (HR 0.77; 95% CI 0.65-0.91) but not nonsmokers (HR 1.02; 95% CI 0.84-1.24). Results were robust to sensitivity analyses excluding the first 2 years of follow-up and when restricted to participants of White European ancestry.
**Clinical Implications:** This large prospective study provides strong evidence that the quality of plant-based diets matters substantially for health outcomes. A healthful plant-based diet — characterized by higher intakes of whole grains, fruits, vegetables, nuts, and legumes, and lower intakes of animal foods, sugary drinks, refined grains, potatoes, and fruit juices — was associated with lower risks of mortality, CVD, and cancer. An unhealthful plant-based diet showed opposing associations with higher risk. Notably, the cardiovascular benefits of a healthful PBD were observed regardless of genetic predisposition to CVD, suggesting broad public health applicability. Unlike strict vegan or vegetarian diets reported in some studies, this flexitarian-style healthful PBD was not associated with increased fracture risk. These findings support dietary guidelines promoting healthful plant-based patterns for chronic disease prevention, though further research in more racially, ethnically, and culturally diverse populations is needed.