Predicting the risk of malignant transformation in pancreatic cyst patients is challenging. We retrospectively investigated the risk factors for malignant transformation in pancreatic cyst patients. Patients with pancreatic cysts diagnosed using imaging tests were followed from November 2008 to December 2021. A significant change was defined as the additional development of high-risk stigmata (HRS), worrisome features (WFs), or pancreatic cancer during monitoring. In total, 479 patients were analyzed, with a median observation period of 50months. Forty-four patients (9.2%) showed significant changes, and eight (1.7%) developed pancreatic cancer. The univariate analysis showed that the cyst diameter at diagnosis (≥ 14mm), main pancreatic duct (MPD) diameter at diagnosis (≥ 3mm), presence of multilocular cysts, and an inconsistent MPD caliber were significant predictive factors for a significant change. One point was assigned for each significant factor. We grouped the patients into three groups: the low-risk group (total score 0), medium-risk group (score 1-2), and high-risk group (score 3-4). The high-risk group had a higher risk of a significant change than the medium- and low-risk groups (age-adjusted HRs for the medium-risk and high-risk groups were 3.0 and 5.2 compared with the low-risk group). Stratification based on risk factors may help predict the development of significant changes in pancreatic cyst patients.