Patients with obstructive hypertrophic cardiomyopathy are presumed to have poor quality of life (QOL) and distress related to their cardiac symptoms and functional limitations. Alcohol septal ablation (ASA) is designed to improve heart function and reduce cardiac symptoms. The purpose of this study was to examine psychosocial factors and QOL in patients with obstructive hypertrophic cardiomyopathy before and 3 months after ASA. Twenty-two adult participants (mean age 57 +/- 14 years, 59% women, 100% Caucasian, 67% married) were recruited during their initial evaluations or scheduled index hospitalizations for ASA. Psychosocial and medical measures were collected before and 3 months after ASA. The results indicated that before ASA, 57% of patients reported clinically relevant levels of depression (Center for Epidemiologic Studies Depression Scale score >16), symptoms of anxiety, and reduced QOL. Repeated-measures analyses of variance revealed that ASA is an effective procedure in reducing disease severity (i.e., peak left ventricular outflow tract gradient, septal thickness, posterior wall thickness) (p = 0.001 to 0.05), depression (p = 0.005), and anxiety (p = 0.029) and improving cardiac-specific QOL (p < 0.001) and generic physical health-related QOL (p = 0.009). Changes in satisfaction with life, optimism, and generic mental health-related QOL were not significant (p = 0.143 to 0.899). In conclusion, significant psychological distress and compromised well-being were present in this sample of pre-ASA patients with obstructive hypertrophic cardiomyopathy. After ASA, significant reductions in psychological distress and improvements in well-being and echocardiographic parameters indicating disease severity were demonstrated. These results suggest that patients perceived broad health benefits from ASA in short-term follow-up.