Patients with sickle cell disease are at risk of vaso-occlusive crises including acute chest syndrome (ACS) and pulmonary hypertension. ACS is a life-threatening complication of sickle cell disease and is associated with increased morbidity and mortality. It is known that pulmonary pressures increase during episodes of acute chest syndrome and may lead to acute right ventricular failure leading to increased morbidity and mortality. Given the paucity of randomized controlled trials, the management of ACS and pulmonary hypertension in the setting of a sickle cell crisis largely relies on expert opinion. We present a case of acute chest syndrome complicated by acute right ventricular failure that was managed with prompt red cell exchange transfusion with favorable clinical outcomes.