Objective: To assess the safety and efficacy of abdominal paracentesis drainage (APD) prior to percutaneous catheter drainage (PCD) in treatment of acute pancreatitis (AP), with the purpose of further optimizing the “step-up” approach for management of AP. Methods: The clinical data of 102 consecutive patients with moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP) treated between June 2009 and June 2011 were retrospectively analyzed. All these patients underwent a “step-up approach”, beginning with conservative treatment, then PCD, and finally open necrosectomy if needed. Of the patients, 53 cases underwent APD prior to PCD (APD plus PCD group), and 49 cases received PCD alone (PCD alone group), and the relevant clinical parameters between the two groups of patients were compared. Results: The baseline data between the two groups were comparable. The fatality rate in APD plus PCD group was significantly lower than that in PCD alone group (3.8% vs. 8.2%, P<0.05); the incidence of infection had no statistical difference between the two groups (P>0.05), but the time to white blood cell recovery, incidence of sepsis as well as time for sepsis recovery, and hospitalization cost were reduced in APD plus PCD group versus PCD alone group (all P<0.05). In addition, comparison of the clinical data 2 d before PCD between the two groups showed that all the levels of inflammatory cytokines and all the scores yielded by different severity scoring systems in APD plus PCD group were lower than those in PCD alone group (all P<0.05). Conclusion: Using APD as a bridging treatment between conservative treatment and PCD for AP is safe and effective, without an increase of infections. APD can reduce the levels of inflammatory factors and incidence of sepsis through effectively evacuating the fluid collections, and thereby improve the prognosis of the patients.