Adequate thromboprophylaxis primarily requires timely detection of reversible and irreversible risk factors of venous thromboembolism (VTE) and their categorization. It is important to note that the highest percentage ofVTE episodes occur in non-surgical (medical) patients and that VTE develops in a large number of surgical patients upon hospital discharge; this emphasizes the need for adequate VTE prevention in inflammatory diseases, acute medical illness and other medical diseases as well as for prolonging and optimizing the anticoagulant regimen after surgical intervention in the primary VTE prophylaxis. As almost completely unrecognized and neglected major risk factors of VTE in clinical practice, we particularly point out the chronic obstructive pulmonary disease (COPD) and heart failure, especially in NYHA functional class III and IV patients with significantly reduced left heart ventricle. It is necessary to raise clinicians' awareness of a potential danger from wrongly and one-sidedly interpreted dyspnea and coughing signs in patients with COPD as typical symptoms of basic respiratory disease as well as from ascribing the signs of disease aggravation in heart failure patients exclusively to cardial status worsening, neglecting the possibility of having unrecognized and untreated pulmonary embolism at issue. Contemporary way of life enhances the development of new VTE risk factors such as traveler's thrombosis, in particular during long-haul flights as well as in individuals sitting at a computer for prolonged periods (e-thrombosis). Determining and recognizing VTE risk factors, especially those formerly neglected nonsurgical ones and simultaneous presence of multiple risk factors within a given period is required for defining an adequate anticoagulant regimen in primary VTE prophylaxis for surgical and non-surgical (medical) patients.