OBJECTIVES: Proper diagnosis of Deep Vein Thrombosis (DVT) at the earliest time is very important so that appropriate therapy can be initiated. Ultrasonography is the most widely used diagnostic technique. Noninvasive magnetic resonance direct thrombus imaging (MRDTI) is a new diagnostic technique that has higher sensitivity and specificity compared to Ultrasonography for distal deep vein thrombosis (DVT). The objective is to identify the most cost-effective strategy for diagnosis of distal deep vein thrombosis. METHODS: A decision-analysis model was constructed using TreeAge Pro software and analyzed using second-order Monte Carlo simulation technique. Diagnostic accuracy was calculated using Bayes’ revision method that utilized sensitivity and specificity of the diagnostic tests along with the pretest probability of developing the disease. Outcomes considered were costs, adverse events and quality of life. Quality-adjusted life years were calculated using life expectancy tables. Where applicable, costs in pounds were converted to US dollars and adjusted through use of Consumer Price Index data from Bureau of Labor Statistics. Net benefit of each strategy was analyzed at different willingness to pay (WTP) thresholds ($0 to $150,000) to determine the most cost-effective strategy. RESULTS: Noninvasive MRI is the optimal strategy for diagnosis of distal DVT at all WTP thresholds greater than $25,000. No diagnosis strategy was the most cost-effective strategy when threshold was below $25,000. Sensitivity analysis showed that noninvasive MRI remained cost-effective even when all costs were varied by 25%. The model results were affected by the sensitivity of the diagnostic tests. CONCLUSIONS: For base-case scenario, noninvasive MRI is the most cost-effective strategy. Considering the cost-effectiveness and the fact that ultrasonography has higher mortality compared to noninvasive MRI, employing noninvasive MRI appears to the optimal strategy. Healthcare providers should consider patient population distribution among the risk groups defined by Wells score for generalizing the study results to their setting.