In the United States, Pneumocystis jirovecii (PCP) is a leading cause of morbidity and mortality in hospitalized patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and can result in severe hypoxemia despite maximal conventional ventilator support. We present 2 adult patients with HIV/ AIDS and PCP who were managed with extracorporeal membrane oxygenation (ECMO) because of refractory hypoxemia. After prolonged hospitalization, the first patient developed multiorgan failure, and the decision was made to withdraw life support. The second patient required ECMO for 7 days and survived. We also review 2 previously published cases in which ECMO was used in adult HIV patients with severe hypoxemia from PCP. In the patients that survived, ECMO was initiated earlier in the course of hospitalization compared with those that died (mean 3.5 vs. 15 d). Furthermore, the patient that survived required a much shorter duration of ECMO support (mean 5.5 vs. 41.5 d). The use of ECMO early in the course of hospitalization can be considered in patients with HIV/AIDS and refractory hypoxemia due to PCP.