We report a case of pulmonary embolism (PE) in an Afro-Caribbean man following a short commercial flight of less than 5,000 kilometers (Km) in economy class with a 1-month interval between journeys. He had an elevated body mass index (BMI) and sickle cell trait (SCT) with hyperhomocysteinemia. No other preexisting source of venous thrombosis was found. We posit that venous thromboembolism (VTE) and/or PE may have been a complication of SCT in an individual with other multiple risk factors. We discuss the possible interaction of these risk factors for VTE and/or PE and the implications for travelers at risk. The need for a PE risk score and guidelines for the prophylaxis of thromboembolism among travelers exists.