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Background: Pancreatic adenocarcinoma remains a challenging malignancy with a poor prognosis. Radiofrequency ablation (RFA) has emerged as a potential treatment for unresectable pancreatic adenocarcinoma (UPAC) aimed at improving survival and quality of life. This meta-analysis and systematic review evaluates the outcomes of RFA in UPAC. Methods: A comprehensive search was conducted in MEDLINE, Embase, Scopus, and Cochrane Central databases from inception to October 2023. Studies included patients over 18 years with UAPC undergoing RFA. Survival rates and complication rates were assessed as primary outcomes. Data were pooled using random-effects models, and heterogeneity was assessed with I2 statistics. ROBINS-I tool was used for quality assessment. Results: Nine studies encompassing 265 patients met the inclusion criteria. The mean age was 64.5 years, with 42.5% female participants. Survival analysis showed that at 30 days post-RFA, the mortality rate was 3.3%. At 6 months, the mortality rate was 20.9%, increasing to 50.4% at 12 months. At 24 months, the mortality rate was 61.9%. The pooled mean survival period at 12 and 24 months was 9.18 months and 14.26 months, respectively. Overall, 78.4% of patients died during the follow-up period, with an overall mean survival period of 12.27 months. The most common were intra-abdominal (10.1%), pancreatic (9.8%), and hepatobiliary (6.7%) complications. Conclusions: RFA shows potential in the management of unresectable pancreatic adenocarcinoma, with a manageable safety profile. However, the high heterogeneity and risk of bias in available studies highlight the need for well-designed randomized controlled trials to confirm these findings and establish standardized protocols. [ABSTRACT FROM AUTHOR]