Background: We examined the influence of cholesteryl ester transfer protein TaqIB polymorphism on triglyceride (TG) response to an oral fat tolerance test (OFTT) in patients heterozygous for familial hypercholesterolemia (hFH). Methods: We genotyped 67 hFH patients (32 men and 35 postmenopausal women) who were subjected to an OFTT. Results: All B1 allele carriers had lower high-density lipoprotein cholesterol (HDL-C) levels (p=0.013) and higher postprandial TG response at 6 and 8 h (p=0.05 and p=0.04, respectively) compared to B2 allele carriers. Multiple regression analysis showed that in the hFH group with a positive response, the presence of the B2 allele was significantly related to lower levels of TG-area under the curve (AUC) (p<0.01) compared to B1, adjusting for age, gender and body mass index. In the hFH group with a negative response, although age and female gender had a significant effect on TG-AUC levels (p<0.01 for both), the allele type was not significantly related to the TG-AUC levels (p=0.99). Conclusions: B2 carriers had a lower postprandial TG response compared to B1 carriers. There were no differences in TG levels between B1 and B2 carriers in patients with a negative OFTT response. Therefore, at higher TG concentration, the B2 allele may protect against an exaggerated postprandial TG increase and subsequent lowering of HDL-C.