The data on iatrogenic atrial septal defect (iASD) after left atrial appendage closure (LAAC), especially intracardiac echocardiography (ICE)-guided LAAC, are limited. Compared with transesophageal echocardiography (TEE)- or digital subtraction angiography (DSA)-guided LAAC, the transseptal puncture (TP) ICE-guided LAAC is more complicated. Whether or not ICE-guided TP increases the chances of iASD is controversial. We investigate the incidence, size, and clinical outcomes of iASD after ICE-guided LAAC. A total of 177 patients who underwent LAAC were enrolled in this study and were assigned to the ICE-guided group (group 1) and the TEE- or DSA-guided group (group 2). Echocardiography results and clinical performances at months 2 and 12 post-procedure were collected from the electronic outpatient records. A total of 112 and 65 patients were assigned to group 1 and group 2, respectively. The incidence of iASD at follow-up (FU) month 2 was comparable between the groups (21.4% in group 1 vs. 15.4% in group 2, p = 0.429). At month 12 of FU, the closure rate of iASD was comparable to that of group 2 (70.6% vs. 71.4%, p = 1.000). No right-to-left (RL) shunt was observed among the iASD patients during the FU. Numerically larger iASD were observed in group 1 patients at month 2 of FU (2.8 ± 0.9 mm vs. 2.2 ± 0.8 mm, p = 0.065). No new-onset of pulmonary hypertension and iASD-related adverse events were observed. Univariable and multivariable logistic regression analysis showed that ICE-guided LAAC was not associated with the development of iASD (adjusted OR = 1.681; 95%CI, 0.634-4.455; p = 0.296). The ICE-guided LAAC procedure does not increase the risk of iASD. Despite the numerically large size of the iASD, it did not increase the risk of developing adverse complications.