Abstract Objective Health-related quality of life (HRQOL) after coronary interventions (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty) usually improves in patients, but not in all patients. Some patients actually show a significant decline in HRQOL. Our aim was to explore the potential of psychologic well-being (anxiety, depression), vital exhaustion, Type D personality, and socioeconomic position as predictors of HRQOL in patients with coronary disease. Methods A total of 106 patients scheduled for coronary angiography were interviewed before (baseline) and 12 to 24 months after coronary angiography. Socioeconomic status was evaluated by education. The General Health Questionnaire 28 was used for measuring psychologic well-being (anxiety, depression), the Maastricht interview was used for measuring vital exhaustion, and the Type D questionnaire was used for measuring personality. HRQOL was assessed using the Short Form-36 (physical and mental components) questionnaire. Functional status was assessed with a combination of New York Heart Association and Canadian Cardiovascular Society classifications. Linear regressions were used to analyze data. Results A change in physical HRQOL was predicted by baseline psychologic well-being (β = −.39; 95% confidence interval [CI], −1.00 to −.16) and baseline HRQOL (β = −.61; 95% CI, −.83 to −.34). A change in mental HRQOL was predicted by (baseline) psychologic well-being (β = −.37; 95% CI, −.99 to −.09), vital exhaustion (β = −.21; 95% CI, −.69 to −.03), and baseline HRQOL (β = −.76; 95% CI, −1.03 to −.44). Ejection fraction did not significantly predict HRQOL. Conclusion Psychosocial factors (psychologic well-being, vital exhaustion) seem to be more important predictors of change in HRQOL compared with some objective medical indicators (ejection fraction) among patients with coronary disease.