BACKGROUND & AIMS: The association between dietary fat and mortality remains inconsistent, and recent results for the association between dietary saturated fat and chronic disease are controversial. To quantitatively assess this association, we conducted a meta-analysis of prospective cohort studies. METHODS: The PubMed and Web of Science were searched up to February 2020. A random effects model was used. RESULTS: Nineteen studies including 1,013,273participants and 195,515deaths were identified. Significant inverse associations between all-cause mortality and a 5% energy increment in intakes of total (RR = 0.99; 95% CI:0.98-1.00), monounsaturated (RR = 0.98; 95% CI:0.97-0.99), and polyunsaturated fat (RR = 0.93; 95% CI:0.89-0.97) were found. A 5% increase in energy from polyunsaturated fat was associated with 5% (RR = 0.95; 95% CI:0.91-0.98) and 4% (RR = 0.96; 95% CI:0.94-0.99) lower mortality from CVD and cancer, respectively. A 1% energy increment in dietary trans-fat was associated with 6% higher risk of mortality from all-causes (RR = 1.06; 95% CI:1.01-1.10) and CVD (RR = 1.06; 95% CI:1.02-1.11). We found a non-linear association between dietary saturated fat and all-cause mortality showing a significant increased risk up to 11% of energy from saturated fat intake. The risk of cancer mortality increased by 4% for every 5% increase in energy from saturated fat (RR = 1.04; 95% CI:1.02-1.06). CONCLUSIONS: Diets high in saturated fat were associated with higher mortality from all-causes, CVD, and cancer, whereas diets high in polyunsaturated fat were associated with lower mortality from all-causes, CVD, and cancer. Diets high in trans-fat were associated with higher mortality from all-causes and CVD. Diets high in monounsaturated fat were associated with lower all-cause mortality.