OBJECTIVES: To investigate factors influencing initial pharmacotherapy for patients with dyslipidemia in primary care setting. METHODS: Dyslipidemia patients were identified from a large US national database of electronic medical records containing diagnosis, lab and medication information in primary care setting from 1997 to 2004. Initial pharmacotherapy was defined as the 1st-antidyslipidemics prescribed if no antidyslipidemics were given 12-month prior to the initiation. Logistic regression models used to examine impact of patient demographics, clinical characteristics, and comorbidities on three outcomes: whether 1) any antidyslipidemics; 2) statin in particular; or 3) combination therapy was initiated. RESULTS: Total 16,578 patients included in analysis. Male and older patients were more likely to initiate any antidyslipidemics than females (odds ratio (OR): 1.14) and younger patients (OR: 3.72 for over 65- vs. under 40-years). Higher LDL-C and triglyceride (TG), and lower HDL-C were associated with higher probability of initiating any antidyslipidemics. Patients with coronary heart disease (CHD) (OR: 1.60), diabetes (OR: 2.42), hypertension (OR: 1.19), other atherosclerotic disease (OR: 1.52), and obesity (OR: 1.10) were more likely to initiate any antidyslipidemics than those didn't have those co-morbidities. Among patients who started pharmacotherapy, those with higher LDL-C or CHD or diabetes were more likely to be on a statin; however, lower HDL-C and higher TG were associated with lower likelihood of initiating a statin. Higher TG level (500+ mg/dL) was the only significant predictor for use of combination therapy among antidyslipidemic users at diagnosis. CONCLUSION: High LDL-C, CHD and diabetes were strong predictors of initiating any antidyslipidemic agents, and statins in particular for patients with dyslipidemia. That patients with abnormal HDL-C or TG were less likely to use statins might reflect perceptions about ineffectiveness of statins in treating these abnormalities. Further studies are needed to assess long-term use patterns of antidyslipidemics and associated outcomes in clinical practice.