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The aim of this prospective study was to compare the feasibility, technical success rate and complication between single-step endo-ultrasonography (EUS)-guided and two-step EUS-guided drainage technique for symptomatic pancreatic pseudocyst (PP).Twenty-one PP patients with clear intra-cystic fluid that needed to be drained were divided into two groups, depending on the availability of the therapeutic echoendoscope at the time of the procedure: Group 1 (13 patients) underwent a single-step EUS-guided endoscopic drainage and Group 2 (8 patients) underwent a two-step EUS-guided drainage technique.In Group 1 immediate technical success was achieved in 92.3% (12/13); two patients had recurrent PP and both were successfully treated by a second EUS-guided drainage. Clinical success was achieved in all cases. In Group 2 technical success was achieved in 75.0% of the patients (6/8). One patient (12.5%) bled 36 h after the procedure. Five out of 6 patients had long-term success. Clinical success was significantly greater in Group 1 (P < 0.05).The technique of single-step EUS-guided drainage was superior to the technique of a two-step EUS-guided drainage technique for PP drainage.