Objectives As a potentially preventable severe event, venous thromboembolism can lead to malpractice claims. We aim to identify characteristics of claimed events and to assess possible association between guidelines compliance and professional liability. Methods We analyzed every claim of alleged medical negligence following venous thromboembolism registered at the Catalan Council of Medical Colleges from 1986 to 2014. Results A total of 100 claims related to venous thromboembolism were identified. In 24 cases, out of 95 closed-claims, medical professional liability was the outcome. The specialty with more complaints was Orthopaedic Surgery. In 43 cases, venous thromboembolism occurred in low-risk patients with no prophylaxis prescribed. Professionals’ conduct followed the official guidelines in 73 cases but still 11 of them ended up in professional liability. Nevertheless, liability outcome was significantly associated with non-compliance of guidelines, as well as the absence of a prophylaxis ( p < 0.001). Conclusions Guidelines should be considered not only a patient safety measure but also a relevant issue towards determining the standard of care required in law. However, guidelines compliance does not qualify automatically as an affirmative defense in claims. It is individualized prophylaxis and protocols compliance that makes clinical practice safe and at the same time avoids medical professional liability.