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Purpose: The health benefits of the Mediterranean diet (MedDiet) have been widely studied. However, controversy remains for one of its components: alcohol intake. We aimed to assess the joint effect of adherence to the MedDiet and alcohol-drinking pattern on all-cause mortality. Methods: We used data from 20,506 subjects from a prospective cohort of Spanish university graduates, the Seguimiento Universidad de Navarra (SUN) cohort. Adherence to the MedDiet was operationalized using four different dietary indexes and then categorized in low or high adherence, according to the median score. Alcohol-drinking pattern was evaluated with the previously defined the Mediterranean alcohol-drinking pattern (MADP), grouped into three categories of adherence (low, moderate and high adherence) and a fourth category for abstainers. The outcome was all-cause mortality. Results: During a median follow-up of 12.1 years, we observed 460 deaths. No statistically significant supra-multiplicative interaction between the two exposures was found. Low adherence to both the MedDiet and MADP was associated with higher all-cause mortality compared to high adherence to both exposures [multivariable-adjusted hazard ratio (HR) = 2.02, 95% confidence interval (CI): 1.33–3.07]. Similar results were found for cancer mortality and cardiovascular mortality. Conclusions: Although the combined effect of the MedDiet and MADP was not significantly higher than the product of their individual effects, a low adherence to both the MedDiet and MADP was associated with higher rates of all-cause mortality. This report also shows the usefulness of the dietary pattern approach applied to alcohol intake and of including the drinking pattern as another component of the MedDiet. [ABSTRACT FROM AUTHOR]