This study was to explore the association between dietary polyunsaturated fatty acids (PUFAs) consumption and cardiovascular diseases (CVDs), all-cause mortality, and CVD-specific mortality.This retrospective cohort study extracted demographic and clinical data of 38,838 adult participants from the National Health and Nutrition Examination Survey (NHANES) database in 2003-2018. We explored the association between octadecadienoic acid (ODA), octadecatrienoic acid (ALA), octadecatetraenoic acid (ODTA), eicosatetraenoic acid (AA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) and different CVDs using weighted univariate and multivariate logistic regression analyses with odds ratio (OR) and 95% confidence interval (CI). The PUFAs were divided into four levels according to the quartiles (≤ Q1, Q1 to Q2, Q1 to Q2, > Q3). Weighted univariate and multivariate COX regression analyses with hazard ratio (HR) and 95% CI were used for exploring the association between PUFAs and all-cause mortality, CVD-specific mortality and other cause-specific mortality.During the follow-up, a total of 4,908 (9.12%) eligible participants died. The results showed that after adjusting for covariates, ODTA intake was related to low odds of coronary heart disease (CHD) [OR = 0.75, 95%CI: (0.64-0.88)]. Q1-Q2 quartile of ALA [OR = 0.81, 95%CI: (0.66-0.99)] and Q2-Q3 quartile of DPA [OR = 0.78, 95%CI: (0.62-0.99)] intakes were linked to low odds of heart attack, and > Q3 quartile of ODA intake was associated with low odds of congestive heart failure (CHF) [OR = 0.66, 95%CI: (0.49-0.90)] and stroke [OR = 0.65, 95%CI: (0.47-0.90)]. Q2-Q3 quartile of DPA intake was linked to low odds of angina [OR = 0.76, 95%CI: (0.58-0.99)]. Higher ALA intake was associated with a lower risk of all-cause mortality [Q2-Q3: HR = 0.86, 95%CI: (0.74-0.99); > Q3: HR = 0.76, 95%CI: (0.63-0.91)]. Additionally, Q2-Q3 quartile of ALA, Q1-Q2 quartile of AA and DPA intakes were respectively related to a low risk of CVD-specific mortality, while that > Q3 quartile of ALA related to that of mortality by other causes.Our study found that PUFAs were associated with different CVDs, and higher ALA intake was related to lower risk of all-cause mortality. Ensuring adequate intake of PUFAs was beneficial to the health and may decrease the risk of mortality.© 2023. BioMed Central Ltd., part of Springer Nature.