Objectives: The aim of this study was to determine whether the application of a CT-based preplanning algorithm might allow abstaining from TEE during LAAC. Background: LAAC is an established treatment alternative for patients with atrial fibrillation. Today, most LAAC procedures are guided by TEE, which, however, leads to the need for patient sedation and might even cause direct harm to the patient. CT-based preplanning of the LAAC procedure, in combination with technical improvements in device design and interventional experience, might allow abstaining from TEE. Methods: Fluoro-FLX is a prospective single-center study to evaluate how often TEE leads to a procedural change during interventional LAAC if a dedicated CT planning algorithm is applied. The study hypothesis is that under these circumstances, a sole fluoroscopy-guided LAAC is an alternative to a TEE-guided approach. All procedures are preplanned by cardiac CT and, finally, guided by fluoroscopy only, while TEE is carried out in the background during the intervention for safety reasons. Results: In none of the 31 consecutive patients did TEE lead to a change in the preplanned fluoroscopy-guided LAAC (success ratio: 1.00; CI: 0.94–1.00), thereby meeting the primary endpoint (performance goal: 0.90). There were no procedure-related adverse cardiac or cerebrovascular events (no pericardial effusion, TIA, stroke, systemic embolism, device embolism, death). Conclusions: Our data suggest that it is feasible to perform LAAC under sole fluoroscopic guidance if preplanning is performed using cardiac CT. This might be worth considering, especially in patients who are at high risk for TEE-related adverse events.