Deep vein thrombosis (DVT) is a major vascular disorder with significant morbidity and mortality. Inherited thrombophilia defects and acquired risk factors both contribute to its pathogenesis. Familial clustering suggests a strong genetic component, but data from Libyan families are limited. This study aimed to investigate inherited and acquired risk factors for DVT in a multigenerational Libyan family with a history of venous thrombosis. We recruited 10 family members: four symptomatic individuals, three asymptomatic individuals, and three controls. The index case had heterozygous factor V Leiden. We analyzed blood samples collected between October 2024 and January 2025 for fibrinogen, factor V, factor VIII, protein C, protein S, D-dimer, and complete blood count parameters. Body mass index and smoking status were also recorded. Factor V deficiency and elevated factor VIII were each observed in 6/10 participants. Elevated factor VIII was present in all four symptomatic patients. Fibrinogen was elevated in 2/10 participants, both asymptomatic. Protein C deficiency was found in 2/10 participants, and Protein S deficiency in; all were symptomatic. D-dimer was elevated in only one symptomatic patient. Obesity was present in 8/10 participants, and smoking in 3/10, all of whom were symptomatic males. However, between-group comparisons did not reach the significance level. These preliminary findings suggest that inherited thrombophilia factors, particularly factor V deficiency and elevated factor VIII, may contribute to DVT susceptibility in this family, with modifiable risk factors possibly acting as triggers.