Risk profiling in deep vein thrombosis (DVT) has been classically concerned with traditional factors of obesity, postoperative status, prolonged recumbency, longstanding varicosity, etc., with subsequent stagnation of blood and damage to vascular endothelium. Only recently, there has been increasing concern with procoagulant factors as protein C, protein S, antithrombin III deficiencies as well as elevated factor VIII, hyperhomocysteinemia, dysfibrinogenemia, etc., all of heredofamilial nature. The present study is intended to assess the prevalence of two genetic disorders promoting coagulation; namely, the mutant form of factor V (Leiden) and the prothrombin gene in Egyptian patients with acute DVT. We studied 30 patients admitted with acute DVT (16 male, 14 female, mean age 44 ± 14 years), and 30 control subjects (19 males, 11 females, mean age 37 ± 10 years). Excluded from the study were patients known to have bleeding diathesis, those with acute or chronic liver disease, and those on oral or parenteral anticoagulation. Following clinical evaluation including 12-lead ECG and routine laboratory tests, all patients were subjected to venous duplex and gene identification. The latter comprised DNA extraction, PCR amplification, and gene mutation detection using the THROMBOTYPE reagent kit. Compared with control subjects, patients with acute DVT had significantly higher prevalence of factor V Leiden Gene mutation (66.7% vs 23.3%, P = 0.003). Compared with noncarriers of this mutant form, carriers exhibited significantly more frequent familial incidence (55% vs 15%, P = 0.035), younger age of presentation (40 years vs 51 years, P = 0.048) and more frequent complications (55% vs 10%, P = 0.049). Prothrombin gene mutation was exhibited by three out of 30 patients with acute DVT (10%) and was associated with factor V Leiden in two of them. None of the control subjects exhibited this mutant form of the prothrombin gene. In conclusion, acute DVT among young patients and particularly those with recurrent DVT should urge the cardiologist to search for factors promoting coagulation. Our data show abnormally high prevalence of the mutant form of factor V Leiden (associated with prothrombin gene mutation in a minority). Besides the diagnostic value, gene mutation detection has therapeutic and prognostic implications through the need to adjust the dose and the duration of oral anticoagulation.