Cardiovascular disease (CVD) in the HIV population accounts for a large proportion of morbidity and mortality and, with the increased life expectancy, the burden of CVD is expected to rise. Inflammation, immune dysfunction, side effects of HIV medications, high prevalence of other risk factors are the likely pathogenic mechanisms for accelerated atherosclerosis. We aimed to evaluate the diagnostic yield of a cardiovascular multimodality diagnostic work-up in a contemporary cohort of HIV-infected patients. From November 2017 to October 2019, HIV infected patients were screened in a cardiovascular diagnostic work-up program including clinical history, physical examination, arterial blood pressure measurement, 12-lead ECG, and Transthoracic Echocardiogram (TTE). Advanced non-invasive cardiovascular imaging tests, like Coronary Computed Tomography Angiography (CCTA), stress-echocardiography, Cardiac Magnetic Resonance (CMR), were performed in patients with suspicion of chronic coronary syndrome (CCS) or non-ischemic heart disease (NIHD). 117 HIV-infected consecutive patients underwent this cardiovascular diagnostic work-up and were included in our study. Fifty-two patients (45%) had evidence of CVD. Of them, 22 presented Coronary Artery Disease (CAD), whereas 47 cases showed NIHD. In 17 cases both conditions were present. Among patients with CAD, 8 showed critical coronary stenosis; among them, 5 were treated with percutaneous coronary intervention, 2 with Aorto-Coronary By-Pass Grafting (CABG), and one with medical therapy. Hypertension and diabetes were significantly associated with the development of CVD (respectively p<0.001 and p< 0.05), while current smoking (p<0.02) and hypertension (p<0.007) were positively associated to CAD. A comprehensive cardiovascular diagnostic work-up including advanced multimodality diagnostic imaging modalities led to early detection of CVD in nearly half of an HIV population with immediate interventions required in 6.8% of them, and aggressive prevention treatment started in the remaining HIV patients.