Objective: The objective of this study was to evaluate the effectiveness of a telephone-based intervention on psychological distress among patients with cardiac illness. Methods: We recruited hospitalized patients surviving an acute coronary syndrome with scores on the Hospital and Anxiety Depression Scale (HADS) indicating mild to severe depression and/or anxiety at I month postdischarge. Recruited patients were randomized into either an intervention or control group. Intervention patients received up to six 30-minute telephone-counseling sessions focused on identifying cardiac-related fears. Control patients received usual care. For both groups, we collected patients' responses to the HADS and to the Global Improvement (CGI-I) subscale of the Clinical Global Impressions (CGI) Scale at baseline and at 2, 3, and 6 months postbaseline using Interactive Voice Recognition (IVR) technologies. We used mixed-effects analysis to estimate patients' changes in CGI-I measures over the three time points of data collection postbaseline. Results: We enrolled 100 patients, and complete CGI-I measures were collected for 79 study patients. The mean age was 60 years (standard deviation = 10), and 67% of the patients were male. A mixed-effects analysis confirmed that patients in the intervention group had significantly greater improvements in self-rated health (SRH) between baseline and month 3 than the control group (p = .01). Between month 3 and month 6, no significant differences in SRH improvements were observed between the control and intervention groups. Conclusions: Study patients reported greater SRH improvement resulting from the telephone-based intervention compared with control subjects. Future research should include additional outcome measures to determine the effect of changes in SRH on patients with comorbid physical and emotional disorders.