Abstract AIMS: To evaluate the long-term prognostic impact of baseline symptoms in a cohort of hypertrophic cardiomyopathy (HCM) patients. METHODS AND RESULTS: We considered 84 HCM patients symptomatic at diagnosis: 26 (31%) with heart failure (group 1), 34 (40%) with syncope/palpitations (group 2) and 24 (29%) with chest pain (group 3). During a median follow-up of 102 (53-187) months, 25 (30%) patients died/underwent heart transplant (HTx), 14 of 26 (54%) in group 1, 10 of 34 (29%) in group 2 and one of 24 (4%) in group 3. At 12, 60 and 120 months, HTx-free survival rates were 100, 79 and 52% in group 1, vs. 100, 97 and 69% in group 2, vs. 96, 96 and 96% in group 3, respectively (P = 0.008). At multivariate analysis, heart failure [hazard ratio (HR) 2.59, confidence interval (CI) 95% 1.09-6.17, P = 0.032] and left atrium diameter (HR 1.83, CI 95% 1.16-2.89, P = 0.009) emerged as independent predictors of death/HTx, with incremental prognostic power with respect to echo Doppler variables of left ventricular systolic and diastolic dysfunction [area under the curve (AUC) of receiver operating characteristics (ROC) curves at 5 years: 0.90 vs. 0.78, respectively, P = 0.03]. CONCLUSION: Clinical presentation emerged as a relevant prognostic tool in HCM patients symptomatic at onset, as heart failure was associated with a particularly poor outcome. Heart failure and left atrium diameter at diagnosis showed incremental prognostic power compared with echo Doppler assessment of left ventricular systolic and diastolic dysfunction.