In particular clinical scenarios, transthoracic and transoesophageal echocardiography (TEE) have limitations. This study sought to test if intracardiac and intraluminal echocardiography (ICLE), including 2-D, M-mode and Doppler analysis with a miniaturised, multiple-frequency transducer-tipped catheter, is suitable for assessing distinct cardiac and vascular disorders. ICLE was employed in 10 animals using 6 standard approaches. In 12 patients undergoing device closure of patent foramina ovalia (PFO) (n = 6) or atrial septal defects (ASD) (n = 3), or aortic stent implantation (n = 3), interventional procedures were guided by ICLE and, for comparison, also by TEE. ICLE provided enhanced diagnostic information on the aorta, cardiac valves, main pulmonary vessels and both atria and, therefore, added to the diagnostic spectrum of TEE. Especially for guiding interventional procedures (e.g., device closure of atrial septal defects and patent foramina ovalia), ICLE was shown to be helpful. Compared with the conventional approach, the technique reduced fluoroscopy time for device closure procedures: 6.5 min vs. 8.9 min, p < 0.0011. With the patient in a supine position, ICLE was better tolerated than TEE. Complications did not occur, either with ICLE or with TEE. In conclusion, ICLE adds to conventional echocardiography and promises to become a clinical alternative for guiding interventional procedures.