Background: Endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA) is a novel modality in the treatment of solid tumours. The aim of the study is to evaluate the technical feasibility, safety and efficacy of multiple-round EUS-RFA with low ablation power for unresectable pancreatic cancer. Methods: We conducted a retrospective analysis of eleven cases with unresectable pancreatic cancer who underwent EUS-RFA between November 2013 and November 2018. For each lesion, RITA 1500X radiofrequency generator was used to deliver 5.10 watts ablation power for 90 seconds, repeatedly. Eight cases underwent the same procedure one week later. Additionally, one patient with the lesion size of 29.7 mm underwent 8 total sessions of RFA every other week. Results: The procedure was successful in all cases and no major adverse events were observed. The post procedure imaging studies and serum CA19-9 level were performed 1 month after procedure, showing two patients had decreased lesion sizes and five patients had decreased serum CA19-9 level. Follow-up duration ranged 2 to 12 months. The patient who underwent 8 total sessions of RFA survived 12 months after follow-up and showed increased tumour apparent diffusion coefficient (ADC) value and 20% ablated area inside the tumour. Conclusions: A multiple-round ablation with optimal RFA energy could be a technically feasible, safe and short-term efficacy option for those patients with unresectable pancreatic cancer.