Introduction: Dietary recommendations promote low-fat rather than full fat dairy consumption. Emerging evidence, however, has raised doubts if avoidance of dairy fat will lower CVD risk. Traditionally, self-reported estimates of dairy fat intake were used to study its relationship with CVD, which are subject to recall biases and measurement error. Here, we employed circulating levels of pentadecanoic acid [15:0] as a biomarker of dairy fat intake to examine its association with CVD incidence and all-cause mortality in a Swedish population-based cohort. We also conducted a systematic review of prospective studies that assessed 15:0, and other dairy fat biomarkers (heptadecanoic acid [17:0] and trans -palmitoleic acid [ t 16n-7]) and their associations with CVD and all-cause mortality. Hypothesis: We assessed the hypothesis that higher levels of dairy fat biomarkers 15:0, 17:0 and t 16n-7 would be associated with lower risk of incident CVD events and all-cause mortality. Methods: In a cohort of 60-year old Swedish women (n=2133) and men (n=2017), we measured 15:0 in serum cholesterol esters at baseline in 1997-99. Cox proportional hazard models were used to assess the associations between serum 15:0 with CVD outcomes and all-cause mortality, after adjusting for demographics and CVD risk factors. In the meta-analysis, five databases were searched to include prospective observational studies that examined the associations between circulating or adipose tissues levels of 15:0, 17:0 and t 16n-7 and CVD and mortality risks. Pooled associations of each dairy fat biomarker with incidence of CVD and all-cause mortality were estimated using a random-effects model. Results: During a median follow-up of 16.6 years, 578 incident CVD events and 676 deaths were identified using national registers. In multivariable-adjusted models, higher serum 15:0 was associated with lower incidence of CVD in a linear dose-response manner [HR: 0.75 per interquintile range; 95% CI: 0.61, 0.93), but in a non-linear relationship with all-cause mortality (P _nonlinearity = 0.03); with a nadir of mortality risk around the median level of 15:0. In the meta-analysis including our Swedish cohort and 17 other studies, the relative risk of total CVD comparing the highest versus the lowest tertile was 0.88 (0.78, 0.99) for 15:0 (n=17), 0.86 (0.79, 0.93) for 17:0 (n=12), and 1.01 (0.91, 1.12) for t16n-7 (n=6). In meta-analyses of ≤3 studies, there was little evidence that dairy fat biomarkers were associated with all-cause mortality. Conclusion: In conclusion, our de novo Swedish cohort study and an updated systematic review including 18 studies suggests that higher levels of dairy fat biomarkers (15:0 and 17:0) were associated with a lower risk of CVD incidence. These results justify further investigation in interventional and experimental studies to elucidate the potential causality of these relationships and relevant mechanisms.