Introduction: Venous thromboembolism (VTE) is a common comorbid condition found in sickle cell disease (SCD) and is associated with increased mortality for adults with SCD. The pathophysiology that leads to the thrombophilic state in SCD has been previously reviewed; however, evidence-based guidelines to aid in diagnosis, prevention, and management of VTE are lacking. Areas covered: This review article will cover the pathophysiology underlying the hypercoagulable state, the epidemiology of VTE, and management strategies of VTE in SCD. Expert opinion: Providers should have a high suspicion for diagnosing VTE to help reduce morbidity and mortality in the SCD population. Unlike other thrombophilias, the risk of life-threatening anemia while being treated with anticoagulation is compounded with the potential complications surrounding red blood cell transfusions in this population (i.e. alloimmunization, hyperhemolysis) and this provides another complexity to managing VTE in this population. Clinical trials evaluating the risk and benefit of treatment and treatment duration are needed.