After reports from observational studies suggesting an association between acutely ill medical patients and venous thromboembolism (VTE), interventional trials with anticoagulants drugs have demonstrated a significant reduction of VTE during and immediately after hospitalisation. Although several guidelines suggest the clinical relevance of reducing this outcome, there is a low tendency to use anticoagulants in patients hospitalised for acute medical illness. We speculated that such underuse may be dependent on a low perception that patients included in the trials are actually at risk of thromboembolism. Therefore, the aim of this study was to analyse the clinical settings included in the interventional trials and their relationship with thrombotic risk. Analysis of interventional trials revealed that the majority of patients included in the trials (about 80%) were affected by heart failure, acute respiratory syndrome or infections. Among these three illnesses, literature data shows an association with venous thrombosis only in patients with acute infections; this finding was, however, supported only by retrospective study. On the contrary, there is scarce or no evidence that heart failure and acute respiratory syndrome are associated with venous thrombosis. These data underscore the need of better defining the thrombotic risk profile of acutely ill medical patients included in interventional trials with anticoagulants.