OBJECTIVES: To assess the cost-effectiveness of D-dimer compared with imaging techniques (current practice) in the diagnostic process of pulmonary embolism (PE) and deep vein thrombosis (DVT) in Colombia. METHODS: Two decision-tree economic models were developed to assess the cost-effectiveness of high sensitivity D-dimer compared with images, for the exclusion of PE and of DVT, in adult patients with low and intermediate probability, according to the pre-test assessment evaluated by the Wells’ scale. The model parameters were obtained from a literature review and validated by an expert panel. Imaging techniques were high-resolution computed tomography and lung scintigraphy for PE and Doppler ultrasound for DVT. The time horizon was one year; we used a third party payer perspective. Costs were estimated in 2015 Colombian pesos 1 EUR = 3041 COP. RESULTS: For the diagnosis of PE, the average estimated cost was €895 with D-dimer and €956 with the imaging technique. D-dimer represented a savings of €61, and had less false positive and false negative rates. For the diagnosis of DVT, the estimated average cost was €306 with D-dimer and €300 with the imaging technique. Despite the slightly higher cost, it again had less false positive and false negative rates. One-way and probabilistic sensitivity analyses showed similar results under most scenarios tested. CONCLUSIONS: The economic model developed for PE shows that highly sensitive D-dimer is a dominant alternative in patients with low and intermediate probability of PE, and is probably cost-effective in patients with low and intermediate probability of DVT, when compared with imaging techniques in Colombia.