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Although seizures have been reported with tramadol use, the exact mechanism is not yet confirmed. An individual genetic susceptibility may have a role in developing seizures. The purpose of this study was to investigate the frequency of mutant allele of the OPRM A118G and MDR1 C3534T in tramadol users with seizures.After investigators obtained informed consent and when other causes of seizures were excluded, 74 Egyptian tramadol users, with and without seizures, were assessed clinically, radiologically, and by electroencephalogram. Their blood samples were genotyped for the µ-opioid receptor gene and the multidrug resistant (MDR1) genes.Thirty-seven subjects had seizures. A history of head trauma and more opioid use were reported by the group with seizures. Family history of epilepsy was present in 2 subjects with seizures. There was no significant difference between the 2 groups with regard to the frequency of occurrence of the SNP A118G of the mu opioid receptor gene or the SNP C3435T of the MDR1 gene.This study could not illustrate a potential genetic background in the studied point mutations that could explain the development of tramadol-induced seizures.