Red blood cell omega-3 fatty acid (FA) levels (the omega-3 index, O3I) are inversely associated with increased risk for cardiovascular (CV) events and has been proposed as a new risk factor. The factors that determine the O3I are not well described. We collected demographic information and measured the O3I in 704 outpatients. The use of fish oil capsules and the reported intake of tuna and other non-fried fish were used to estimate omega-3 FA intake. A multiple linear regression model was constructed to explore influences on the O3I. The subjects were 67% male with a BMI of 28±6 and an age of 62±12 years. Capsules were being taken by 34%, 13% were smokers and 16% were diabetic. The significant predictors of O3I in decreasing order were: supplement use, eating non-fried fish, age, BMI, and smoking. Gender and diabetes were not significant predictors. The model explained 52% of the variation in the O3I, with capsules/fish intake together accounting for 47%. The O3I increased by 12.5% with each category of fish intake in the non-supplementers, and by 17.5% (both p<0.0001) for those taking supplements. Those consuming the most fish and taking capsules had an O3I of 7.5±1.8% compared to 2.4±0.7% at the opposite extreme. In conclusion, the intake of fish oil capsules and oily fish were the principal determinants of the O3I but together explained only about half of the variability in this marker. Support: St. Luke's Hospital Foundation.