Background/objectives <p>Evidence supports plant-based diets for preventing cardiovascular diseases (CVD). Fat mass is a strong predictor of CVD, however it is unclear whether this mediates the relationship between plant-based diets and CVD. Thus, this study aimed to determine if longitudinal associations between plant-based diet quality indices and incidence of CVD events, CVD mortality and all-cause mortality were mediated by fat mass in mid-aged adults.</p> Subjects/methods <p>Dietary data (Oxford WebQ) from 14,233 adults from the UK Biobank were used to calculate adherence to three plant-based diet quality indices: an overall plant-based diet (PDI), a healthy plant-based diet (hPDI), and a less healthy plant-based diet (uPDI). Dual X-ray absorptiometry measured percentage fat mass. Cox proportional hazard ratios (95% CI) identified associations between the indices and CVD events, CVD mortality or all-cause mortality, and mediation analyses determined overall, direct, and indirect effects of fat mass.</p> Results <p>The PDI and hPDI were inversely associated with fat mass, and the uPDI was positively associated (<i>p</i> &lt; 0.001). In several models, fat mass was associated with CVD events, CVD mortality, and all-cause mortality after controlling for the plant-based diet quality indices. No association was found between the indices and health outcomes, with (direct effect) or without (total effect) the fat mass mediator (<i>p</i> ≥ 0.1). In several models there was a significant negative indirect effect for the PDI or hPDI on CVD events or CVD mortality via the fat mass mediator, and a significant positive indirect effect for the uPDI on CVD events and CVD mortality.</p> Conclusions <p>No evidence was found for an association between the plant-based diet quality indices on the outcomes without, as well as after accounting for fat mass. However, the significant indirect effects found suggest that fat mass may be a key mechanism linking plant-based diets to CVD.</p>