Background: Mucosal perforation during laparoscopic esocardiomyotomy is quite frequent, and its consequences cannot always be neglected. The purpose of the study is to investigate the risk factors for intraoperative mucosal perforation and its implications on the postoperative outcomes and the functional results three months postoperatively. Material and methods: We retrospectively identified the patients with laparoscopic esocardiomyotomy performed at Sf. Maria Hospital Bucharest, in the period between January 2017–January 2022 and collected the data (preoperative—clinic, manometric and imaging, intra-and postoperative). To identify the risk factors for mucosal perforations, we used logistic regression analysis. Results: We included 60 patients; intraoperative mucosal perforation occurred in 8.33% of patients. The risk factors were: the presence of tertiary contractions (OR = 14.00, 95%CI = [1.23, 158.84], p = 0.033206), the number of propagated waves ≤6 (OR = 14.50), 95%CI = [1.18, 153.33], p < 0.05), the length of esophageal myotomy (OR = 1.74, 95%CI = [1.04, 2.89] p < 0.05), the length of esocardiomyotomy (OR = 1.74, 95%CI = [1.04, 2.89] p < 0.05), and a protective factor—the intraoperative upper endoscopy (OR = 0.037, 95%CI = [0.003, 0.382] p < 0.05). Conclusions: Identifying risk factors for this adverse intraoperative event may decrease the incidence and make this surgery safer. Although mucosal perforation resulted in prolonged hospital stays, it did not lead to significant differences in functional outcomes.