Chronic use, overdose and withdrawal are potential causes of seizures in illicit substance abusers. The aim of this work is to assess the pattern of substance abuse in patients presented with new onset seizures. Eighty patients presented to Mansoura Toxicology Unit and Neurology Department with a history of substance abuse and witnessed attack of seizure for the first time were included in the study. The mean age of patients was 25.9 ± 6.5 years and most of them were men. Substance abuse-related seizures were mostly associated (78.75%) with tramadol either alone or in combination with opiate and /or cannabis. There is a significant correlation regarding age and pattern of substance abuse-related seizures. Multi-substance abuse is more prevalent (66.25%) than single drug intake in all age groups. It could be concluded that seizures are a common serious complication in substance abusers and should not be underestimated especially with tramadol either alone or in combination with opiates and or / cannabis. Raising the awareness of general population and medical personnel regarding the seizure potential and the misconception about tramadol safety is warranted.