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Objectives: This study compares the progression of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs) to unifocal (UF) lesions., Methods: We performed a retrospective review of demographics, risk factors, and cyst characteristics of a prospectively maintained database of 999 patients with pancreatic cysts. Patients included had IPMN under surveillance for 12 months or more. Those with high-risk stigmata were excluded. Cyst size progression and development of worrisome features were compared between MF and UF cohorts. We evaluated whether the dominant cyst in MF-IPMN had more significant growth than did the other cysts., Results: Seventy-seven patients with MF-IPMN and 54 patients with UF-IPMN, with mean follow-up of 27 and 34 months, met the criteria. There were no significant differences between demographics, risk factors, or initial cyst sizes. Fifty-seven percent of MF dominant cysts and 48% of UF cysts increased in size (P = 0.31). Progression in MF was more likely in the dominant cyst (P < 0.05). There were no significant differences in the development of mural nodules or increase in cyst size to more than 3 cm., Conclusions: Demographics of both cohorts were similar, as was the overall incidence of worrisome features. Because meaningful size progression primarily occurred in the dominant cyst, our findings support surveillance based on the dominant cyst in MF disease.