BACKGROUND Debate surrounding the role of fibrates has followed mixed outcomes from several randomised controlled trials. Subgroup analysis of even the negative trials reveals significant reduction in cardiovascular risk amongst patients with low HDL-C and high TG. We previously described factors associated with HDL-C change following fibrates. As fibrates influence both HDL-C and TG levels via their action on PPAR-α, we now wished to study TG change following fibrate therapy and any associations with baseline and change in HDL-C and TC levels. METHODS Data was collected from case notes of patients started on fibrates (n=248) between 2002 and 2008 in the lipid clinics at Heart of England NHS Foundation Trust. Regression analyses were carried out to determine factors associated with changes in TG. RESULTS Multiple regression analysis revealed that TG change was associated with pre-treatment TG (p<0.001) and TC levels (p=0.029). The association between TG change and pre-treatment TG remained significant when all factors including gender, concurrent statin treatment, diabetes and baseline HDL-C were entered into the regression model. Our previous study demonstrated significant post-fibrate HDL-C change in the group with baseline HDL-C values <1.0mmol/l. In our present study significant TG reduction was observed regardless of the baseline patient characteristics including HDL-C levels. CONCLUSIONS The actions of fibrates are considered to be mediated via PPAR-α, but our data suggest that the effects on TG and HDL-C are different. Thus, the mechanisms mediating the changes of these lipids following fibrate treatment may vary.