Background: Diagnosis of venous thromboembolic disease (deep venous thrombosis and pulmonary embolism) is often inaccurate because signs and symptoms are nonspecific. Numerous clinical management trials using D-dimer which is one of the coagulation markers have shown that it has a sufficient specificity to assist in the diagnosis of venous thromboembolic disease. Aim of the work:This study was done to validate the utility of D-dimer as a diagnostic biomarker for DVT using a higher cutoff values which may improve the test specificity. Material and method: In this retrospective chart review study, we reviewed the hospital records of all patients for whom D-dimer assay was done in King Abdul Aziz Specialist Hospital, Al Taif - Saudi Arabia from January 2011 to October 2013. The study involved 141 individuals; 25 who were proved to be normal were chosen to serve as control group (Group I), 61 patients who were positive for DVT by duplex scanning (Group II) and 55 patients who had symptoms of DVT but showed negative results on duplex ultrasound(group III). Results: The demographic data revealed statistically insignificant difference between all studied groups. No significant differences were detected between the studied groups, except for hemoglobin level which was significantly lower in patients of groups II and III than in control group. However, highly significant differences were detected between different studied groups as regards D-dimer. Analysis of the receiver operator characteristic (ROC) curve to establish the cutoff level of the studied marker in the diagnosis of DVT, verified that D-dimer value of 0.92 mg/L can accurately differentiate patients who were positive for DVT on duplex scanning from control group. Level of 2.81 mg/L for D-dimer was considered as a cutoff point that can differentiate patients who were duplex negative and free from thrombosis from those who eventually developed thrombosis. Conclusion: This study suggests the importance of the use of modified D-dimer cut-off values that can safely differentiate patients who are free from venous thromboembolic disease from others who are positive for the disease sparing patients the unnecessary risks of anticoagulation. In addition it can detect the patients who will eventually develop thrombosis regardless their primary duplex ultrasound scanning results, so, they could receive anticoagulation treatment.