Psychological distress and negative conditions are highly frequent in patients with percutaneous coronary intervention (PCI). Mindfulness-based stress reduction (MBSR) has been shown to be effective in reducing psychological symptoms in patients with chronic diseases. The available evidence has supported the potential benefit of MBSR for PCI patients. However, the traditional group classroom format and long exercise times of MBSR were deemed as barriers to access for these patients. The aim of this study was to examine the short-term effectiveness of a brief, one-on-one, telephone-adapted MBSR on psychological distress of PCI patients. A randomized controlled trial was conducted. Seventy consecutive PCI patients who met the inclusion criteria were randomized to a three-session mindfulness intervention group (N = 35) or a waitlist control group (N = 35). The Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS), and short form of the Freiburg Mindfulness Inventory (FMI-s) were used to assess anxiety and depression, stress, and mindfulness before and after the intervention. Sixty-two patients completed the study. Compared with the waitlist group, the MBSR group showed greater decreases in HADS (p = .006) and PSS (p = .035) scores. The intention-to-treat (ITT) analysis also demonstrated that HADS (p = .018) and PSS (p = .037) scores decreased significantly in the MBSR group compared with those in the waitlist group at Week 6. These effects were mediated by an increase in mindfulness. The brief, one-on-one, telephone-adapted mindfulness intervention can improve psychological symptoms in PCI patients.