Objective: Proper diagnosis of Deep Vein Thrombosis (DVT) at the earliest time is very important so that appropriate therapy can be initiated. Various diagnostic tests have been developed for DVT, but most of them have poor sensitivity and specificity. Due to the above issues, it is very important that diagnosis strategies be developed which are cost-effective. Methods: Cost-effectiveness was analyzed using a decision model from TreeAge Pro Suite 2007 software. Outcomes considered were costs, adverse events and quality adjusted life years (QALYs). Probabilities were calculated using Bayes' revision method that utilized sensitivity and specificity of the diagnostic tests along with the pretest probability of developing the disease. Quality of life and costs data were pooled from literature reviews. QALYs were calculated using life expectancy tables. Costs in pounds were converted to US dollars and adjusted through use of Consumer Price Index data from Bureau of Labor Statistics. Results: With a cost-effectiveness ratio of $32.4995 per QALY, the following strategy dominated other alternate strategies - Perform venography if D-dimer test is positive. Otherwise, if D-dimer test is negative then no treatment is given. If venography shows abnormal results, treatment is given otherwise for normal results, no treatment is given. Sensitivity analysis showed that this strategy remained cost-effective even when all costs were varied by 25%. The model results were affected by the sensitivity of the diagnostic tests. Conclusion: Based on this analysis, it would be cost-effective if symptomatic patients are diagnosed with the strategy after classifying them according to Wells score. Further research needs to be done to see if cost of venography is offset by decrease in hospitalization of those who later develop severe form of DVT. Healthcare providers should consider patient population distribution among the risk groups defined by Wells score before generalizing the finding.