Defective DNA repair has been reported to be a risk factor forvarious malignancies. Polymorphisms of DNA repair genes could alterprotein structure and may impair DNA repair capacity. Geneticpolymorphisms of XRCC1 gene could lead to defective base excisionrepair (BER) pathway resulting in impaired DNA repair capacity andincreased risk of acute leukemia. The aim of this work was to determinethe possible effect of XRCC1 gene polymorphisms 194Arg to Trp and399Arg to Gln on the risk of development of acute leukemia in a group ofEgyptian patients. The study was also extended to evaluate the associationbetween these polymorphisms and disease outcome. Polymorphisms ofXRCC1 codon 194 (Arg to Trp) and codon 399 (Arg to Gln) weregenotyped in 35 patients with acute lymphoblastic leukemia (ALL), 35patients with acute myeloid leukemia (AML) and 70 healthy controls usingpolymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method. The results of the present work revealed that therewas an increased risk of AML among carriers of XRCC1 194Trp and anincreased risk of ALL among patients with XRCC1 399Gln variantgenotypes. Combined presence of XRCC1 194Trp and 399Gln variants(haplotype A) had significantly higher risk of both ALL and AML. Thepolymorphic variants of XRCC1 codons 194 and 399 had significantunfavorable effect on disease outcome of both AML and ALL.