BACKGROUND Coronavirus disease 2019 (COVID-19) is the cause of a pandemic disease, with severe acute respiratory syndrome by binding target epithelial lung cells through angiotensin-converting enzyme 2 in humans. Thus, patients with hypertension with COVID-19 could have worse prognosis. Indeed, angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers may interfere with angiotensin-converting enzyme 2 expression/activity. Thus, patients with hypertension undergoing angiotensin-converting enzyme inhibitor and/or angiotensin receptor blockers drug therapy may be at a higher risk of contracting a serious COVID-19 infection and should be monitored. Moreover, in the present study we investigated the effects of angiotensin-converting enzyme inhibitor versus angiotensin receptor blockers versus calcium channel blockers on clinical outcomes as mechanical ventilation, intensive care unit admissions, heart injury, and death in 62 patients with hypertension hospitalized for COVID-19 infection. METHODS AND RESULTS The multicenter study was prospectively conducted at Department of Infectious Diseases of Sant'Anna Hospital of Caserta, and of University of Campania "Luigi Vanvitelli" of Naples, at Department of Advanced Surgical and Medical Sciences of University of Campania "Luigi Vanvitelli," Naples, and at General Medical Assistance Unit "FIMG," Naples, Italy. Lowest values of left ventricle ejection fraction predicted deaths (1.142, 1.008-1.294, P<0.05), while highest values of interleukin-6 predicted the admission to intensive care unit (1.617, 1.094-2.389), mechanical ventilation (1.149, 1.082-1.219), heart injuries (1.367, 1.054-1.772), and deaths (4.742, 1.788-8.524). CONCLUSIONS Anti-hypertensive drugs didn't affect the prognosis in patients with COVID-19. Consequently, tailored anti-inflammatory and immune therapies in addition to chronic antihypertensive therapy, could prevent a worse prognosis, as well as improve the clinical outcomes in patients with hypertension with COVID-19 infection.