Atherosclerosis is one of the major causes of increased morbidity and mortality associated with coronary artery disease, cerebrovascular accidents, and peripheral vascular diseases. Dyslipidemia is one of the important causes that result in atherosclerosis. The incidence of atherosclerosis has been on the rising recently. Therefore prevention of dyslipidemia can decrease the development of atherosclerosis. Aims: The study was undertaken to determine the efficacy of atorvastatin alone and its combination with omega-3 fatty acids in the management of hyperlipidemia in patients attending a tertiary care hospital. Methods: This study was a cross-sectional prospective study conducted in the Department of Pharmacology and General Medicine, Kakatiya Medical College and Hospital, Warangal. The patients were selected from those visiting General Medicine OPD and diagnosed with hyperlipidemia. Sixty patients in the age group of 20 – 70 yrs, were recruited based on inclusion and exclusion criteria. They were divided into two groups. The Group I included the patients receiving Tab. Atorvastatin 10mg/day and Group II Atorvastatin 10mg/day plus Cap Omega-3 fatty acids 600mg/day for the duration of six months and follow up were done every month. Efficacy of treatment was assessed by the changes in laboratory parameters of Total cholesterol, Triglycerides, HDL-C, LDL-C, and VLDL-C. Results: The efficacy of combination therapy i.e., Atorvastatin plus Omega-3 fatty acids showed a statistically significant rise in HDL cholesterol with the mean percentage difference of 4.24% when compared to monotherapy with Atorvastatin. The efficacy of other parameters like total cholesterol (TC), LDL cholesterol, VLDL cholesterol, and triglycerides (TG'S) levels with the low dose of omega-3 fatty acids in combination therapy was not statistically significant and produced nearly identical alterations in serum lipoprotein levels when compared to monotherapy. Conclusion: Although statins are being used as first-line therapy for hyperlipidemia and in patients with elevated triglycerides. For patients with elevated LDL-C and low HDL-C combination therapy appears to be a better option. Thus omega-3 fatty acids may be a potential supplement for combination therapy apart from niacin and fibrates.