By considering the debilitating outcome of co-occurring of bipolar disorder (BD) and substance abuse, determination of risk factors of substance use disorders (SUD: abuse or dependence of drugs and/or alcohol) is essential to identify the susceptible patients. The purpose of this study was to clarify the major determinant factors of SUD among adults with BD by reviewing the relevant literature. We systematically searched electronic databases including PubMed (MEDLINE), EMBASE, OVID, Cochrane and Scopus for human studies addressing the co-existence of bipolar disorder and SUD. All potential published papers up to September 2016 have been reviewed. The statistical analysis was performed using Comprehensive Meta-analysis version 2. Male gender (Odds ratio: 2.191 (95% CI: 1.121–4.281), P 0.022), number of manic episodes (P: 0.001) and previous history of suicidality (Odds ratio: 1.758 (95% CI: 1.156–2.674), P: 0.008) were associated to SUD in patients with BD. SUD was not related to age, subtype of BD, hospitalization and co-existence of anxiety disorders or psychotic symptoms. SUD affects many aspects of BD regarding clinical course, psychopathology and prognosis. Our study demonstrates that male gender, history of higher number of manic episodes and suicidality are associated to higher susceptibility to SUD. Thus, assignment of more intensive therapeutic interventions should be considered in patients with increased risk of drug abuse to prevent development of SUD.