Background: Recurrent, severe manic or hypomanic episodes characterize bipolar disorder (BD), a chronic mental condition. To be resilient is to be able to keep going even when things are difficult. Aim and objectives: To assess resilience in cases with bipolar disorder (with and without comorbid substance use disorder (SUD)) in relation to personality traits. Subjects and Methods: This was a cross-sectional comparative study performed at the outpatient clinic of Port Said Mental Health and Addiction Treatment Hospital in a time for a year starting from January 2022 to January 2023. 33 BD patients without SUD (Control Group) and 33 BD patients with SUD (Patient Group). Results: There was no statistically significant variance found among the two groups regarding sociodemographic characteristics, social health domain, resilience, SES and EPQ domains. There was a statistically significant association among resilience and medical state. Also, the results showed statistically highly significant correlations between resilience and occupational state, drug/alcohol, legal state, family history, social state, and psychological state. Linear regression analysis predicted that the high the physical health score of QOL, and the reduce the ASI domains (medical, legal, psychological and family history) scores, the higher was the resilience. Conclusion: We concluded that there was a negative impact of SUD on resilience in BD patients. Managing SUD in BD patients together with improving their medical, psychological, legal states and family history all can improve their resilience, and consequently better outcome of BD.