A case is described here of drug-induced immune hemolytic anemia (DIIHA) due to cefotetan administered to a post-partum woman who received the drug for infection prophylaxis at the time of caesarean section. Renewed fatal hemolysis occurred when the drug was given a second time 12 days after the first dose. The initial immunohematologic findings included a positive direct antiglobulin test (DAT) due to IgG and complement coating of the patient's RBCs as well as an eluate that did not react with RBCs in the absence of drug. The antibody was drug-dependent, reacting with both drug-coated RBCs as well as when the drug was added to a mixture of her serum and donor RBCs. Cefotetan has been a common cause of this uncommon problem. The clinical features of cefotetan DIIHA, classification of drug-induced antibodies, and the differential diagnosis of a positive DAT are briefly discussed.