Statins generally increase high-density lipoprotein cholesterol (HDL-C), but not in all patients. This retrospective study was designed to find out the factors related with the differences of HDL-C responses to statin therapy. The patients newly diagnosed as hypercholesterolemia and treated with statin, were enrolled. All patients had received one kind of statins for at least two months. Serum level of total cholesterol (TC), triglycerides (TG), HDL-C, low-density lipoprotein cholesterol (LDL-C) before and after statin therapy were collected. And data of body mass index (BMI), coexistence of diabetes mellitus (DM), hypertension (HTN), coronary artery disease (CAD), cerebrovascular accident (CVA) and prescribed statin and its dose were included in analysis. Total 516 patients (256 males and 260 females) were enrolled. Patients with DM were 199 (38.4%), with HTN were 294 (56.7%), with CAD were 197 (38.0%) and with CVA were 103 (19.9%). The prevalences of DM, HTN, CAD and CVA were not different between the group (decreased HDL-C group) with decreased HDL-C level after statin therapy and the other group (the other group) with preserved or increased HDL-C level after statin therapy. The other group showed the tendency of low HDL-C level (HDL-C < 40 mg/dL for male, < 45 mg/dL for female) at baseline period (p=0.014). Decreased HDL-C group showed more decrease of TC (p<0.001) and LDL-C (p<0.001) and increase of TG (p<0.001). When analyzed by prescribed statins, there was no relation between the kinds of statins and bad HDL-C response. In subgroup analysis by co-morbid diseases, including DM, HTN, CAD, CVA, the result showed no difference in lipoprotein profile change between subgroups. More patients with decreased HDL-C level after statin therapy were observed in patients with CAD (p=0.02). Patients with initial low HDL-C level showed poor responses to statins in terms of TC (p=0.011) but better responses in te! rms of HDL-C than those with initial normal HDL-C level (p<0.001). The risk of HDL-C decrease with statin therapy coexists with large reduction of LDL-C level, so HDL-C raising therapy can be considered with statin therapy, especially in the patients of high risk, such as CAD.