Background: Substance abuse refers to excessive use of a drug in a way that is detrimental to self, society, or both. Substance abuse and its health outcomes has become a major public health issue in Egypt in recent years. Objective: To determine the prevalence of electrocardiographic and echocardiographic abnormalities among substance abusers who have low cardiovascular risk profile and evaluate the relation between these abnormalities and substance abuse. Patients and Methods: This case–control study was conducted at Al-Hussein University Hospital from January 2018 to May 2020. It included 500 males and females cases aged between 18 and 45 years. They were divided into 2 major groups: Group I contained 250 substance abusers with duration of abuse ≥ one year and Group II contained 250 non abusers as controls. All members of both groups had low cardiovascular risk profile. The only major risk factor for heart disease presented in this study was smoking cigarette and its effect was ameliorated by matching with the control group. All cases were subjected to a full history taking, comprehensive clinical examination and laboratory investigations to exclude cases with major risk factors for heart diseases. Cardiac condition was evaluated in all cases using standard 12-lead electrocardiogram and the results were interpreted. Further evaluation using echocardiography examination were done for all patients with abnormal ECG findings in addition to 42 cases selected randomly from control group for statistical purposes, and divided into 2 sub-groups. Sub-group I included 54 patients who had abnormal ECG findings in group I, Sub-group II included 54 cases (12 patients who had abnormal ECG findings + 42 cases selected randomly) from group II. Results: There was significantly higher prevalence of ECG and echocardiographic abnormalities among substance abusers (p < 0.05) in comparison to non-abusers. The most common abnormality detected in substance abusers was QT interval prolongation (6.4%), while the most common echocardiographic abnormality detected was diastolic dysfunction (25.9%). All of abused substances detected in our study (cannabis, tramadol, heroin, alcohol and strox), except benzodiazepines, had significant relation with the abnormal ECG findings. Further analysis for factors related to abnormal ECG findings showed that the increase in duration of abuse, tramadol abuse and heroin abuse were significantly associated with the odds of abnormal ECG findings. Conclusion: ECG and Echocardiographic abnormalities have significant prevalence among substance abusers, especially those with multiple substance abuses, despite of their low cardiovascular risk profile. Long duration of abuse, heroin abuse and tramadol abuse were considered risk factors for abnormal ECG findings.