BACKGROUND & AIMS Previous studies have suggested that some plasma phospholipid saturated fatty acids (SFA) are associated with an increased risk of coronary heart disease and hypertension, major risk factors for heart failure (HF). However, little is known about the association between SFA and HF. This study examines associations of individual plasma phospholipid SFA with HF risk in US male physicians. METHODS The current ancillary study used a prospective nested matched case-control design to select 788 cases of incident HF and 788 controls. Plasma phospholipid SFAs were measured using gas chromatography. HF was self-reported on follow-up questionnaires and validated by review of medical records in a subsample. We used conditional logistic regression to estimate relative risks. RESULTS Mean age was 58.7 ± 8.0 years. One standard deviation higher plasma phospholipid 16:0 was associated with an odds ratio (95% CI) of 1.20 (1.04, 1.38) controlling for established HF risk factors and other SFAs (p = 0.042). However, this association was not significant after Bonferroni correction (p > 0.008). We did not observe associations between other SFAs (14:0, 15:0, 18:0, 20:0, or 22:0) and HF risk (all p for trend > 0.05). CONCLUSIONS Our data suggested no association between plasma phospholipid SFAs and HF in US male physicians.