OBJECTIVE: To simultaneously investigate the association of diet quality and all-cause mortality in groups with varying cardiometabolic diseases (CMDs) at baseline. RESEARCH DESIGN AND METHODS: From the population-based Lifelines cohort, 40,892 non-underweight participants aged ≥50 years with data on diet quality and confounding factors were included (enrollment 2006-2013). From food-frequency questionnaire data, tertiles of the Lifelines Diet Score were calculated (T1 = poorest, T3 = best diet quality). Four CMD categories were defined: 1) CMD free, 2) type 2 diabetes, 3) one cardiovascular disease (CVD), 4) two or more CMDs. Months when deaths occurred were obtained from municipal registries up until November 2019. Multivariable Cox proportional hazards models were applied for the total population and stratified by CMD categories. RESULTS: After a median follow-up of 7.6 years, 1,438 participants died. Diet quality and CMD categories were independently associated with all-cause mortality in crude and adjusted models (P < 0.001). A dose-response relationship of diet quality with all-cause mortality was observed in the total population (Ptrend < 0.001, T2 vs. T3 = 1.22 [1.07-1.41], T1 vs. T3 = 1.57 [1.37-1.80]). In stratified analyses, the association was significant for CMD-free individuals (T1 vs. T3 = 1.63 [1.38-1.93]) and for patients with type 2 diabetes (1.87 [1.17-3.00]) but not for patients with one CVD (1.39 [0.93-2.08]) or multiple CMDs (1.19 [0.80-1.76]). CONCLUSIONS: A high-quality diet can potentially lower all-cause mortality risk in the majority of the aging population. Its effect may be greatest for CMD-free individuals and patients with type 2 diabetes. Tailored dietary guidelines may be required for patients with extensive histories of CMDs.