Stress is important in substance use disorders (SUDs). Mindfulness training (MT) has shown promise for stress-related maladies. No studies have compared MT to empirically validated treatments for SUDs. The goals of this study were to assess MT compared to cognitive behavioral therapy (CBT) in substance use and treatment acceptability, and specificity of MT compared to CBT in targeting stress reactivity. Thirty-six individuals with alcohol and/or cocaine use disorders were randomly assigned to receive group MT or CBT in an outpatient setting. Drug use was assessed weekly. After treatment, responses to personalized stress provocation were measured. Fourteen individuals completed treatment. There were no differences in treatment satisfaction or drug use between groups. The laboratory paradigm suggested reduced psychological and physiological indices of stress during provocation in MT compared to CBT. This pilot study provides evidence of the feasibility of MT in treating SUDs and suggests that MT may be efficacious in targeting stress.