Background <p>A stress test is commonly used as an initial evaluation tool for determining a possible cardiac origin for chest pain. This study was performed to test the hypothesis that patients with a positive stress test will have a significantly lower health-related quality of life (HRQoL) than patients with a negative stress test.</p> Methods <p>This study was a two-group non-experimental design where group assignment was based on the result of the stress test. Participants completed an HRQoL questionnaire (EuroQol-5D) prior to performing the Bruce treadmill stress test. The stress test was considered positive if participants reported chest pain or developed electrocardiogram ST-T changes or arrhythmia during the test.</p> Results <p>A total of 123 participants completed the study with 33 participants with a positive stress test and 90 participants with a negative stress test. Participants with a negative stress test reported a significantly lower (<i>p</i> = 0.014) HRQoL as compared to participants with a positive stress test. In the overall sample, current smokers (<i>p</i> &lt; 0.001) and women (<i>p</i> = 0.02) were found to have a lower HRQoL.</p> Conclusions <p>Patients with non-cardiac chest pain can experience lower HRQoL. The HRQoL was not related to results of the diagnostic testing. This study underscores that patients with non-cardiac chest pain could benefit from additional psychological assessment and treatment.</p>