Objective: To assess the effects of mindfulness-based stress reduction (MBSR) on the mental states, sleep quality, and medication compliance of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). Methods: Altogether 116 patients with AMI after PCI were prospectively studied and randomized into a control group and a research group (n=58 each). Patients in the control group were given conventional nursing, while those in the research group were given MBSR based on conventional nursing. Before intervention and at 7 days after intervention, the patients' mental states, sleep quality, and satisfaction with life were assessed using the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), the Pittsburgh Sleep Quality Index (PSQI), and the Satisfaction with Life Scale (SWLS). Meanwhile, the medication compliance and nursing satisfaction were compared between the two groups. Results: After intervention, the SAS, SDS, and PSQI scores in the research group were lower than those in the control group (all P<0.05), but the SWLS scores were higher than they were in the control group (P<0.05). After intervention, the scores of no drug abuse, medication according to the doctor's advice, and no unauthorized drug withdrawal in the research group were higher than those in the control group (all P<0.05), and the nursing satisfaction was also higher than it was in the control group (P<0.05). Conclusion: MBSR applied in patients with AMI during the perioperative period of PCI is beneficial to regulating their negative emotions, improving their sleep quality, medication compliance, and satisfaction with life, and it enhances the patient-nurse relationship.