Background: Drug-induced immune hemolytic anemia (DIHA) is a rare condition that occurs primarily as a result of drug-induced antibodies, either drug -dependent or drug-independent. The main mechanisms of pathogenesis of drug-induced immune hemolytic anemia are adsorption of the drug onto RBCs, adsorption of immune complexes onto RBCs, RBC membrane modification, and drug-induced autoimmunity. Numerous drugs have been described to cause drug-induced hemolytic anemia or positive direct antiglobulin test (DAT). Aim: Based on this, our aim was to evaluate the association of positive DAT with nonreactive eluate and DIHA. Methods: From 2014 to 2018 we evaluated 159 patients who presented positive DAT with a nonreactive eluate. Laboratory and clinical analyzes were performed including HIV, HBV ad HCV testing. All patients were exposed to drugs: Dipyrone in 63.5%, Furosemide in 28.9%, Metoclopramide in 34.6% and Ondansetron in 41.5%. Results: Antibody screening was positive in 72 (45.3%) of the patients. Results of DAT showed IgG in 125 (78.4%) patients and C3d in 24 (15.1%) with reactions varying from 1+ to 4+. The mean hemoglobin was 8.3 g/dL, hematocrit 25.3%, reticulocytes 1.6%, LDH 576 U/L, total bilirubin 1.7 mg/dL, direct bilirubin 0.7 mg and indirect bilirubin 1.3 mg. HIV test was positive in 10 (16.1%) patients, HBV was positive in 3 (4.7%) and HCV was positive in,1 (1.5%). There was no clinical significance when the parameters of hemoglobin, hematocrit, reticulocytes and LDH were evaluated, only a slight increase in bilirubin especially in the patients with positive DAT reacting 3+/4+ due to IgG and C3d sensitization. Clinical evaluations showed that all patients were asymptomatic. Conclusions: The association of drugs with positive DAT can be a challenge to transfusion services and immunohematology reference laboratories. No case with clinical repercussion of severe hemolysis was evidenced through the clinical and laboratory findings analyzed with the drugs herein associated with positive DAT. Dipyrone and Furosemide have already been associated with DIHA but there are no studies reporting the association of Metoclopramide and Ondansetron with DIHA.