AbstractChanges between diet quality and health-related quality of life (HR-QoL) over 12 years were examined in men and women, in 2844 adults (46 % males; mean age 47·3 (sd 9·7) years) from the Australian Diabetes, Obesity and Lifestyle study with data at baseline, 5 and 12 years. Dietary intake was assessed with a seventy-four-item FFQ. Diet quality was estimated with the Dietary Guideline Index, Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurological Delay Index (MIND) and Dietary Inflammatory Index. HR-QoL in terms of global, physical component summary (PCS) and mental component summary (MCS) was assessed with the Short-Form Health Survey-36. Fixed effects regression models adjusted for confounders were performed. Mean MCS increased from baseline (49·0, sd 9·3) to year 12 (50·7, sd 9·1), whereas mean PCS decreased from baseline (51·7, sd 7·4) to year 12 (49·5, sd 8·6). For the total sample, an improvement in MIND was associated with an improvement in global QoL (β = 0·28, 95 % CI (0·007, 0·55)). In men, an improvement in MIND was associated with an improvement in global QoL (β = 0·28, 95 % CI (0·0004, 0·55)). In women, improvement in MIND was associated with improvements in global QoL (β = 0·62 95 % CI (0·38, 0·85)), MCS (β = 0·75, 95 % CI (0·29, 1·22)) and PCS (β = 0·75, 95 % CI (0·29, 1·22)). Positive changes in diet quality were associated with broad improvements in HR-QoL, and most benefits were observed in women when compared to men. These findings support the need for strategies to assist the population in consuming healthy dietary patterns to lead to improvements in HR-QoL.