Objective: Mindfulness-based stress reduction (MBSR) reduces anxiety among undergraduate students; however, there is limited evidence demonstrating mechanistic underpinnings. Theoretical models implicate cognitive self-regulation as a mechanism. This study explored whether an adapted MBSR embedded in a college course reduced anxiety and if self-regulation mediated any intervention effects. Participants: 144 undergraduate students participated in the study; 34 completed a MBSR course and 110 served as a matched control group. Methods: Mindfulness, self-regulation, and anxiety were measured at pre-MBSR, post-MBSR, and 1-month follow-up. Results: Repeated-measure ANOVAs indicated significant effects of MBSR for self-regulation and anxiety. Longitudinal mediation models indicated significant mediation effects of self-regulation on anxiety at post-intervention and 1-month follow-up. Conclusions: MBSR can be implemented within a college course to indirectly affect anxiety mechanistically via self-regulation. Given increasing rates of anxiety in college students and reduced capacity for counseling centers to meet need, MBSR holds promise for future clinical study.