To evaluate the change in compliance to thromboprophylaxis guidelines before and after the implementation of a multifaceted patient safety program. Longitudinal before and after study. Teaching hospital, Hospital Universitario San Ignacio, Bogotá (Colombia). Adult nonsurgical hospitalized patients. A multifaceted program for the prevention of venous thromboembolic (VTE) disease among adult nonsurgical hospitalized patients. The strategies of the program included (i) update and communication of thromboprophylaxis guidelines, (ii) the implementation of risk-assessment tools in electronic medical records, (iii) nursing staff activities and (iv) education to health personnel and patients for maintenance of the program. Appropriate use of thromboprophylaxis. 221 and 236 patients were evaluated in the pre- and postimplementation periods, respectively. Global appropriate thromboprophylaxis prescription went from 74.66 to 82.6% (P=0.064). Adequate thromboprophylaxis in high-risk patients did not increase significantly (77.70 vs 80.62%, P=0.528), but a significant reduction in inappropriate thromboprophylaxis formulation in low-risk patients was found, decreasing from 20.55 to 5.26% (P=0.005). Implementing a quality improvement multifaceted program improves the formulation of adequate thromboprophylaxis. Reducing the inappropriate prescription of VTE prophylaxis in patients at low risk of thrombosis can lead to a reduction in bleeding complications and a better use of economic and human resources.