Introduction: Transcatheter edge-to-edge tricuspid valve repair (T-TEER) for tricuspid regurgitation (TR) is always guided by TEE. Hypothesis: Safety and efficacy of T-TEER can be increased by multimodality imaging (MMI) guidance. Methods: From December 2020 to January 2022, we performed T-TEER in 40 inoperable patients. All patients received TTE, TEE and cardiac CT screening, and were assigned to a MMI (n=17) guidance group, provided good TTE acoustic window, or otherwise classical TEE (n=23). Multimodality imaging employed the 4 right-sided chamber views. Accordingly, the 1-chamber view was obtained in the transgastric short-axis view on TEE, but also from a modified subcostal TTE short axis. The 2-chamber view was visualized from a low-esophageal position, or from a parasternal long axis view of the right ventricle. The 3-chamber view was seen on mid-esophageal TEE 50-100°, but also in the parasternal short axis view. Finally, the 4-chamber view was obtained on mid-esophageal 0-30°, or the classical four-chamber TTE view. CT derived fluoroscopic angulations of these views allowed interventionalists and imaging specialists to speak a common language. Results: Device success was achieved in all patients, with 1.5±0.6 implanted clips / patient in the MMI vs 1.5±0.5 in the TEE group (p=0.851). Device times were 66.1±35.1 vs 58.7±27.5 minutes (p=0.459). TR reduction was successful in 94% vs 95% of patients, p=1.000. Two- or more grade TR improvement occurred in 65% vs 52% of cases. There were no device associated complications but 3 TEE-related gastro-esophageal bleedings occurred in the 2 nd group. By 12 months, 4 vs 8 patients (p=0.504) were readmitted for acute heart failure, and 2 vs 4 (p=0.686) died. NYHA class decreased by one grade in all survivals. However, Kansas City Cardiomyopathy Questionnaire score and 6-minute walk distance significantly increased in each respective group, more with MMI ( Δ 29±21.4 vs 22±13.6 points, p=0.227; Δ 101±100.4 vs 85±64 meters, p=0.121). Conclusions: A patient-tailored MMI approach to T-TEER guidance, by using TTE in patients with good acoustic window and cardiac CT for fluoroscopic determination of the 4 right-sided chamber views, is feasible and improves safety, procedural success and, in turn, clinical outcomes.