Introduction: Radiotherapy may cause valvular (VHD), pericardial, coronary artery disease (CAD), left ventricular dysfunction (LVD), arrhythmias. The risk of radiation induced heart disease (RIHD) increases over time. The current guidelines suggest a screening for RIHD every 5 years in the long-term survivors who had been treated by chest RT.Methods: We reviewed the clinical and instrumental data of 106 patients diagnosed with RIHD. In one group (Group A: 69 patients) RIHD was diagnosed in an asymptomatic phase through a screening with ECG, echocardiogram and stress test. A second group (37 patients) was seen when RIHD was symptomatic. We compared the characteristics of the two groups at the time of RT, of RIHD detection and at last follow-up.Results: Overall, 64 patients (60%) had CAD (associated to other RIHD in 18); 39 (36.7%) had LVD (isolated in 20); 24 (22.6%) had VHD (isolated in 10 cases). The interval between the last negative test and the diagnosis of moderate or severe RIHD was <5 years in 26 patients, and <4 years in 18. In group A, 63% of the patients with CAD had silent ischemia. The two groups did not differ with regard to type of tumor, cardiovascular risk factors, use of anthracycline-based chemotherapy, age at RT treatment, radiation dose and interval between RT and toxicity detection. The mean time from RT and RIHD was 16 years in group A and 15 in group B. Interventional therapy at RIHD diagnosis was more frequent in group B (54 vs. 30%, p < 0.05). At last follow-up, 27 patients had died (12 of cancer, 9 of cardiac causes, 6 of other causes); mean ejection fraction was 60% in group A and 50% in group B (p < 0.01). Patients with ejection fraction ≤ 50% were 14.5% in group A and 40% in group B (p < 0.01).Conclusions: Clinically relevant RIHD become evident at a mean interval of 16 years after RT. The most frequent clinical manifestations are CAD and LVD. RIHD diagnosis in asymptomatic patients may preserve their cardiac function with timely interventions. We suggest -after 10 years from radiotherapy- a screening every 2–3 years.