Objective:To determine the safety and long-term efficacy of endoscopic ultrasonography-guided lauromacrogol ablation (EUS-LA) for treatment of pancreatic cystic neoplasms (PCNs) with a larger population.Methods:From April 2015 to April 2019, 255 patients suspected of PCNs were enrolled in the First Medical Center of Chinese PLA General Hospital in the study, and 57 patients underwent EUS-LA. The effectiveness of EUS-LA was determined based on imaging volume changes. The occurrence of complications was observed and recorded.Results:Among the 57 patients who underwent EUS-LA, 38 were female and 19 were male, with the mean age of 52.0±14.6 years. The cysts were located in the head/uncinate of the pancreas in 33 patients and in the body/tail of the pancreas in 24 patients. A total of 50 patients were followed up by imaging examinations. After treated by EUS-LA, the cyst median volume sharply reduced from 11 434.1 mm 3 to 639.4 mm 3 ( Z=-5.556, P<0.01), and the median diameter decreased from 32.0 mm to 12.0 mm ( Z=-6.161, P<0.01). Postoperative imaging showed a complete resolution in 24 patients (48.0%), partial resolution in 14 patients (28.0%), and persistent cyst in 12 patients (24.0%). The total number of ablation was 69, and there were 12 patients undergoing a second ablation. The adverse events rate was 4.3% (3/69). Among the 34 patients followed up for 12 months or more, complete resolution was observed in 18 patients (52.9%), partial resolution in 9 (26.5%), and persistent cyst in 7 (20.6%). Conclusion:EUS-LA is effective and safe for the treatment of PCNs. Its effectiveness is stable after more than 12 months′ follow-up.