PURPOSE: The Hospital Anxiety and Depression Scale (HADS) is frequently used by clinicians to assess anxiety and depression in patients with cardiovascular disease; yet, its minimal clinically important difference (MCID) has not been established. The purpose of this study was to establish an MCID for the HADS in patients with cardiovascular disease. METHODS: A sample of 591 patients (74% male; ethnicity = 89% white; mean ± standard deviation [SD]: age = 63 ± 10 yr; and body mass index = 29.1 ± 5.6 kg/m) with cardiovascular disease enrolled in a 3-mo cardiac rehabilitation program were included in this study. The MCID for the HADS was estimated using distribution-based methods (ie, standard deviation, effect size, standard error of measurement, and minimal detectable change), anchor-based methods (ie, health transition question, correlation and linear regression, and receiver operating characteristic curve), and Delphi methodology (ie, clinical consensus). RESULTS: A total of 18 MCID values were calculated ranging from 0.81 to 5.21 (Anxiety subscale) and 0.5 to 5.57 (Depression subscale). The final MCID for the HADS, triangulated from the distribution-based, anchor-based, and Delphi-based findings, was 1.7 points. CONCLUSIONS: Our work provides the first estimates of an MCID by triangulating multiple methodologies for the HADS in patients with cardiovascular disease. This MCID may serve as an indicator of treatment success for clinicians and researchers and guide future interventions to improve the mental health of patients with cardiovascular disease.