This study examines clinical and non-clinical factors associated with treatment compliance problems in 342 patients with substance use disorders (SUD) seen in routine psychiatric practice. Weighted Wald-X(2) and multivariate logistic regression assessed sociodemographic, clinical, treatment, and health plan characteristics associated with treatment compliance problems. Among patients with SUD, 40.5% were reported to currently have treatment compliance problems. Patients with treatment compliance problems were significantly more likely to have personality disorders, lower global assessment of functioning scores, and medication side effects than those without treatment compliance problems. Patients seen by psychiatrists who were reimbursed by discounted rather than undiscounted fee-for-service were five times more likely to be reported to have treatment compliance problems. Both clinical and non-clinical factors appear to be associated with treatment compliance problems. Understanding these factors and targeting treatment interventions may improve treatment compliance and patient outcomes.