The 2015-2020 Dietary Guidelines for Americans (DGA) was issued in early 2016. It remains untested if adherence to these guidelines could reduce mortality risk. Using a modified version of the 2015 Dietary Guidelines for American Index (2015 DGAI), we investigated if adherence to the new DGA is associated with mortality in a Spanish (the Seguimiento Universidad de Navarra, SUN) cohort. We assessed the habitual diet of 16,866 participants of this cohort recruited between 1999 and 2014 and calculated their adherence scores to the new DGA using the modified 2015 DGAI (0-21 points). Mortality data was determined from the yearly National Death Index reports. After adjusting for demographic and lifestyle confounders, high adherence scores (fourth quartile) were found to be associated with reduced all-cause, cardiovascular and cancer mortality risk, hazard ratios (HR) (95% confidence intervals [CI]) 0.42 (0.25-0.70), 0.30 (0.10-0.90) and 0.46 (0.22-0.96), respectively, compared to low adherence scores (first quartile). A 2-point increase in the 2015 DGAI score was linearly inversely associated with all-cause mortality (HR [95% CI] 0.78 [0.67-0.92]). Main sources of variability in the adherence scores were whole-fat dairy products, red/orange vegetables, fresh fruits, red meat, and dark green vegetables. In conclusion, higher adherence to 2015-2020 Dietary Guidelines for Americans was inversely associated with total, cardiovascular and cancer mortality risk in a Spanish cohort.