Metabolic studies have clearly shown that trans fatty acids (TFAs) elevate LDL and lower HDL cholesterol. Epidemiologic studies showed a relation between TFA intake and the risk of myocardial infarction (MI), but studies examining adipose tissue TFAs have not uniformly confirmed this. We performed a case control study examining both adipose tissue levels and dietary intake of TFAs and first MI. Between 1995 and 1997, 209 cases of first MI completed a 300-item FFQ and 79 had an adipose tissue biopsy; 179 matched controls completed the FFQ and 167 had a biopsy. During the course of the study (mid-1996), TFAs were eliminated from margarines sold in Australia. Cases biopsied before mid-1996 had greater levels of trans 18:1(n-9) (32% P < 0.03) and trans 18:1(n-11) (23%, P < 0.001) than controls biopsied before mid-1996. After June 1996, there were no differences between cases and controls in any of the adipose tissue TFAs measured. Logistic regression showed that trans 18:1(n-11) (P = 0.03) was an independent predictor of a first MI. Cases consumed 0.5 g/d (P = 0.002) more TFAs than controls. Subjects in the highest quintile of TFA intake had an OR for first MI of 2.1 (95% CI, 1.1-4.3), which was not independent of saturated fat intake. Apparent TFA intake from margarine was related to adipose tissue 18:1t[(n-9) and (n-10)] in 1995 (r = 0.66, 0.66, respectively). We conclude that TFAs in adipose tissue are associated with an increased risk of coronary artery disease and rapidly disappear from adipose tissue when not included in margarines.