Introduction: Recent studies have suggested that HDL efflux capacity could be a potentially beneficial assay to predict the risk of cardiovascular diseases (CVDs), compared to HDL cholesterol (HDL-C) levels. Recently, we developed a novel methodology using high-performance gel permeation chromatography (HPLC) to evaluate lipoprotein particle number of each subclass. In this study, we investigated CETP-deficient (CETP-D) patients, who are elevated in HDL-C levels, but not likely to be protected from atherosclerosis as we reported previously. Hypothesis: To evaluate lipoprotein particle number of each subclass may be also useful to predict the risk of CVDs. Methods: Nine CETP-D patients, whose serum CETP mass was less than 0.1μg/mL, were compared with 9 normolipidemic controls. Free cholesterol, cholesteryl ester, triglyceride and phospholipid levels in each 20 lipoprotein subclass were determined by computer-assisted HPLC. Furthermore, we calculated the particle number of each subclass by using HPLC data and serum apolipoprotein levels, which is newly-developed LipoSEARCH® system (Skylight Biotech Inc, Akita). Results: As we reported previously, serum HDL-C levels were markedly elevated in CETP-D patients compared with controls. The number of very large and large HDL particles in CETP-D patients was markedly higher than that in controls (4237.3±2353.4nM vs 213.4±55.7nM, 7672.2±1368.3nM vs 1720.2±536.6nM, respectively; p<0.001), while the number of small and very small HDL, which have anti-atherogenic function, was significantly lower (4339.1±937.4nM vs 5690.3±467.8nM, 1999.4±514.8nM vs 3256.5±294.0nM, respectively; p<0.001). The number of large and medium LDL was significantly lower in CETP-D patients than that in controls (158.3±36.4nM vs 240.6±51.1nM, 349.1±69.9nM vs 557.3±94.8nM, respectively; p<0.001), whereas the number of very small LDL, which is known to be atherogenic, was significantly higher (233.2±64.8nM vs 171.4±22.1nM, p=0.016). Conclusions: We have investigated particle numbers of each lipoprotein subclass in CETP-D patients. Our data might indicate that CETP deficiency leads to pro-atherogenic lipoprotein profile.