Objectives: Attention deficit hyperactivity disorder (ADHD) and substance use disorders (SUD) are overrepresented among incarcerated populations. We examined whether ADHD was associated with increased severity of comorbid SUD and with increased psychiatric comorbidity among prisoners. Methods: Cross-sectional study of 500 randomly selected Latino male prisoners in the Puerto Rico Correctional System using validated diagnostic measures to assess Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) ADHD and SUD diagnosis, antisocial personality disorder (ASP) and borderline personality disorder (BPD), major depression, and generalized anxiety disorder (GAD). We defined SUD severity by symptom count and by presence of at least 2 current SUD diagnoses (polysubstance). Results: Participants with ADHD had increased risk for lifetime (p < 0.05) and current (p < 0.01) SUDs, all comorbid psychiatric disorders , and suicidality (p < 0.001). They had more severe SUD, both in number of symptoms and number of SUD (polysubstance) diagnoses (p < 0.01). ADHD was associated with increased psychiatric comorbidity, as participants with ADHD were more likely to have a second diagnosis, and a greater number of comorbid disorders (p < 0.001). ASP, BPD, major depression, and GAD, but not ADHD, were significant predictors of SUD severity in adjusted models. Conclusions: Findings highlight the complex mental health needs of incarcerated populations, where SUD, ADHD, and other psychiatric disorders are prevalent and interrelated.