OBJECTIVEOur study aimed to assess the association between all-cause mortality and the most prevalent chronic diseases in Spain, including diabetes mellitus.DESIGNPopulation-based retrospective cohort study. SITE: Spanish population (Spanish National Health Survey).PARTICIPANTSA population numbering 14,584 respondents of both sexes aged 40 years or older was selected.MAIN MEASUREMENTSThe outcome variable was all-cause mortality over 6-year follow-up, measured by probabilistic cross-matching with the national death registry. Socioeconomic variables, health indicators, service use, and behavioral factors were collected. The main data source was the National Statistics Institute.RESULTSOf the 14584 people included, 1346 (9.2%) died over 6-year follow-up. Regarding the most prevalent chronic diseases, those showing the strongest association with mortality were cancer (HR 1.74, 95% CI 1.40-2.16); chronic lung diseases (chronic obstructive pulmonary disease, bronchitis, or emphysema; HR 1.44, 95% CI 1.19-1.70); acute myocardial infarction (HR 1.33, 95% CI 1.08-1.65); and diabetes (HR 1.23, 95% CI 1.06-1.42). Less prevalent chronic diseases also increased mortality risk, including cirrhosis/liver disease (prevalence 1.5%; HR 1.67, 95% CI 1.22-2.29) and cerebrovascular diseases, including embolism and stroke (prevalence 2%; HR 1.39, 95% CI 1.07-1.81).CONCLUSIONSChronic diseases affect over half the population aged 40 years and older in Spain. Some of the most prevalent conditions are closely associated with all-cause mortality. These include chronic lung diseases, acute myocardial infarction, and diabetes. Given their impact on mortality in the population, more efforts are needed in chronic disease prevention and management.