An increased rate of seizures due to tramadol poisoning has been observed. However, the actual incidence and related factors are not well-studied. The purpose of this work was to investigate the relationship between the incidence of seizures and plasma tramadol level in patients with tramadol-inducing seizures. In addition, we reported the pattern of tramadol overdoses in selected patients. The study was conducted from 1 st January 2017 to 28 th February 2018. It involved 102 cases who recruited from toxicological units of Al-Azhar University Hospital (New Damietta). After free informed consent to contribute in this study and within one hour after arrival to a toxicological unit, 10 mL of blood were separated and the serum was used for extraction of tramadol residues by using a highperformance liquid chromatography (HPLC) and other blood samples were stored at _ 8 o C for the following assays to all patients; fasting blood sugar, hemoglobin levels, serum urea, serum creatinine and liver enzymes. Then clinical examination to all patients included vital signs with a special attention to central nervous system (CNS) manifestations, gastrointestinal (GIT) manifestation. The frequency of seizures (27.4%) with acute tramadol poisoning in humans is not dose dependent and seizures occurred with therapeutic doses and there were no relation between blood tramadol level and seizures. We concluded that risk of seizures increase in cases took other drugs with tramadol as alcohol and heroin. The frequency of seizures is not dose dependent; seizures occurred with therapeutic doses.