OBJECTIVE Amyloidosis is a systemic disease, related to different underlying causes, with frequent cardiac involvement. Clinical evaluation, echocardiography and electrocardiography represent important noninvasive tools in identification of cardiac involvement. The aim of this study was to assess the clinical-laboratory features of a series of patients affected by cardiac amyloidosis in order to evaluate the risk of cardiac mortality. METHODS We evaluated 48 patients (men 65%, mean age 63 ± 11 years) with biopsy-proven diagnosis of amyloidosis and heart involvement observed from 1991 to 2009. All patients underwent clinical-laboratory evaluation at baseline and were followed up. RESULTS During a median follow-up of 9.5 months (first to third interquartile: 3-41.5 months), 24 patients (50%) died as a result of a cardiac cause. Survival free from cardiac death was 69, 50, 48 and 41% at 6, 12, 24 and 60 months from diagnosis, respectively. At multivariable Cox regression analysis, the presence of heart failure at enrolment [hazard ratio (HR) 4.67, 95% confidence interval (CI) 1.07-20.27, P = 0.04] and history of recent syncope (HR 3.97, 95% CI 1.28-12.34, P = 0.017) emerged as independent predictors of cardiac death. By using the equation derived from the multivariate analysis, individual survival probability at different times of follow-up was calculated. CONCLUSIONS We confirm the particularly poor outcome of cardiac amyloidosis in the short term. A careful clinical evaluation emerges as the most important tool for the prognostic stratification and quantification of risk in patients with cardiac amyloidosis.