Clostridium perfringens infection is rarely complicated by severe hemolysis caused by the microbial alpha-toxin, a phospholipase. Patients with this complication usually have a hepatobiliary or colonic source of infection. The mortality rate is extremely high when massive hemolysis supervenes, and the duration of illness from symptom onset to death is often only hours. We describe a patient with a liver abscess, C perfringens bacteremia, and massive hemolysis with severe multiorgan failure. He survived with supportive treatment including aggressive transfusion of packed red cells, systemic antibiotics, and surgical intervention. A literature review disclosed 45 cases of arbitrarily defined massive hemolysis, with 41/45 (91.1%) mortality and a median survival time of 6 hours from symptom onset in those patients who died. There were no reported survivors in cases of hemolysis due to C perfringens septicemia of the severity seen in our patient. A search of the area pathology service database identified 132 cases of C perfringens bacteremia during the period January 2001 to December 2016. Although there were no well-confirmed (by laboratory testing) cases of massive hemolysis in these patients, 4 of 132 patients (3%) died suddenly with blood samples that were not analyzed because of marked visual hemolysis.