Hypertrophic cardiomyopathy (HCM) is a common hereditary heart disease associated with heart failure and sudden death. Quality of life and psychological distress were found to be impaired in HCM patients but have never been assessed in mutation carriers, with or without manifest HCM. We aimed to assess quality of life and psychological distress, using standardized questionnaires, and to identify sociodemographic, clinical, risk and illness perception related predictors thereof in 228 HCM mutation carriers. HCM carriers' overall quality of life and distress scores did not differ from the Dutch population. Quality of life and distress were worst in carriers with manifest HCM before DNA testing and best in predictively tested carriers without HCM. The latter group had even significantly better quality of life than the general population. Substantial determinants of impaired physical quality of life were symptoms (beta = 5.2, P = 0.001) and stronger belief in serious consequences of carriership (beta = 3.5, P < 0.001); determinants of impaired mental quality of life were physical comorbidity (beta = 3.0, P = 0.020) and a higher perceived risk of symptoms (beta = 0.9, P = 0.001). Female gender (beta = 1.4, P = 0.004) and stronger emotional reactions (beta = 1.2, P = 0.002) were associated with more anxiety. Less understanding of carriership (beta = 0.9, P = 0.007) and stronger belief in serious consequences (beta = 0.8, P = 0.008) increased depression. Levels of quality of life and distress were not impaired compared to the Dutch population. Illness and risk perception related variables were major determinants of quality of life and distress. Because these variables can be addressed and adjusted during pre- and post-test counseling, genetic counseling should focus on these determinants.