Objectives: This study aimed to assess the rate of difficult interatrial septum (IAS) crossing with the intracardiac echocardiography (ICE) probe during percutaneous left atrial appendage (LAA) closure and to identify techniques that facilitate IAS crossing with the ICE probe. Background: Percutaneous LAA closure is increasingly performed by ICE guidance. Although such an approach omits the need for general anesthesia, crossing of the IAS with the ICE probe may sometimes be challenging. Methods: All consecutive patients that underwent ICE-guided percutaneous LAA closure with an Amplatzer Amulet (Abbott) or WatchmanFLX (Boston Scientific) at our center in the period 2018–2021 were included. Cases in which IAS crossing with ICE was difficult were identified and techniques used to facilitate IAS crossing were identified and listed. Results: In 17 (5%) out of 354 cases, IAS crossing with the ICE probe was difficult and required use of additional techniques. Ultimately, IAS crossing was also successful in these 17 cases by using one of three possible facilitation techniques: the probing technique (12 cases), the double-wire technique (3 cases), and the snaring technique (2 cases). In one case, the double-wire technique was converted to the snaring technique, as crossing of the ICE probe remained challenging despite the use of two stiff guidewires. Conclusion: Crossing of the IAS with the ICE probe can be challenging in 5% of ICE-guided percutaneous LAA closure procedures. Operators should be aware of possible facilitation techniques in challenging cases, as these show to be safe and effective.