Abstract Background and Aim Different studies have shown pharmacogenetic variants related to drug toxicity in acute myeloid leukemia (AML) patients. Our aim was to identify the association between ABCB1, CDA , DCK , GSTT1 , and GSTM1 variants with clinical outcomes and toxicity in pediatric patients with AML. Methods Fifty‐one confirmed de novo AML pediatric patients were included. A SNaPshot™ assay and conventional PCR were used to evaluate ABCB1, CDA , DCK , GSTT1 , and GSTM1 variants. Clinical outcomes and toxicity associations were evaluated using odds ratios and Chi‐square analysis. Results Patients carrying ABCB1 (1236C > T, rs1128503) GG genotype in had a 6.8 OR (CI 95% 1.08–42.73, p = .044) for cardiotoxicity as compared to patients carrying either AA or GA genotypes 0.14 OR (CI 95% 0.023–0.92, p = .044). For ABCB1 (1236G > A rs1128503/2677C > A/T rs2032582/3435G > A rs1045642) AA/AA/AA combined genotypes had a strong association with death after HSTC OR 13.73 (CI 95% 1.94–97.17, p = .009). Combined genotypes GG/CC/GG with CDA (79A > C, rs2072671) CA genotype or CDA (‐451G > A, rs532545) CT genotype, had a 4.11 OR (CI 95% 2.32–725, p = .007) and 3.8 OR (CI 95% 2.23–6.47, p = .027) with MRD >0.1% after first chemotherapy cycle, respectively. Conclusion Our results highlight the importance of pharmacogenetic analysis in pediatric AML, particularly in populations with a high degree of admixture, and might be useful as a future tool for patient stratification for treatment.