BACKGROUND Treating deep vein thrombosis (DVT) using a once-daily dose of enoxaparin offers greater convenience and the possibility of home-based care for certain patients, as opposed to a continuous infusion of unfractionated heparin (UFH). The study aimed to determine the most cost-effective thromboprophylaxis between low-molecular-weight heparin (LMWH) and UFH for hospitalized patients. METHODS After obtaining clearance from the institutional ethical committee, the study was conducted in the Department of General Surgery, Sri Devaraj Urs Medical College, over a period of six months. Informed consent was obtained from all 46 patients included in this study. The participants were divided into two groups: group A received LMWH and group B received UFH. RESULTS The mean age in group A was 59.8 + 10.6 years and in group B was 54.9 + 12.3 years. There was no significant difference in the girth of the lower limb between the groups during the follow-up period (p > 0.05). In group A, there was a highly significant reduction in lower limb girth from day one to day five (p < 0.0001), day five to day 10 (p < 0.0001), and day one to day 10 (p < 0.0001). In group B, there was no significant reduction from day one to day five (p = 0.06), but there was a significant reduction from day five to day 10 (p = 0.001) and day one to day 10 (p = 0.001). CONCLUSIONS Treatment with LMWH as an anticoagulant significantly reduced the lower extremity girth and thrombus thickness in cases of DVT when compared to UFH.