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Substance use disorder is a major health problem that affects the community, across various ages’ groups and is not restricted to certain sex. The prevalence of substance use among Egyptians has been increased since the 1970s. According to the WHO (WHO, 2010), the prevalence of drug dependence in individuals between 15 and 64 years of age in Egypt was 0.8%. Resilience has been extensively studied as is one of many factors which affect people’s mental health and undertaking risky behaviors. Evidence suggests that resilient people have a better mental health status; have greater self-regulatory skills; higher self-esteem; greater parental support; and are less likely to get involved in high-risk behaviors such as drug abuse. This study aimed at to determine whether there is a difference in resilience between substance users and Non-users. The mean age for cases was 32.63+8.85 years while of the control was 32.87+8.14 years .The age of cases and control showed no statistical difference (P=0.914). Most of the cases and control (70%) were from age group (21-39 years ). All of the & control were male, this is due to all patients attending to outpatient clinic were male no female cases, both groups were from urban areas, the control was mainly from Cairo and Giza, while the cases from port Saied and Domeate. There was no statistical difference between control and cases as regard marital status. However, 56.7% of cases were single, There was a statistical significance difference between cases and control as regard the level of education (P<0.001), where the control obtained high level of education, (university graduates), whereas most of the cases obtained middle level of education (technical institutes) With respect to drug use, the mean number drug use by individual was 2.41+1.64 substance, with minimum of one drug and maximum of 7 drugs. Twenty one cases (72.4%) were poly-users, while only 8 cases were using one drug. Hashish and tramadol reported to be the most frequent drugs used (73.3%). When comparing the combined resilience score for each clusters of questions , the control group showed a higher statistical significant resilience score as regard personal competence ,trust in one’s instinct and positive acceptance compared with cases P<0.05. On the other hand, there were no significant difference in resilience regarding control and spiritual influences P>0.05. However, when comparing the total resilience score for control with that of cases, the control was significantly higher in resilience than cases P<0.05.