BACKGROUND We aimed to investigate the clinical efficacy of continuous renal replacement therapy (CRRT) in combination with peritoneal lavage for the treatment of severe acute pancreatitis. MATERIAL AND METHODS We retrospectively reviewed data from 52 patients with severe acute pancreatitis between January 2014 and December 2021 at Jiangyin People's Hospital. The patients were divided into 2 groups: CRRT (n=26) and CRRT in combination with peritoneal lavage (n=26). The following results and outcomes were retrospectively compared: procalcitonin, interleukin-6, and C-reactive protein levels, duration of systemic inflammatory response, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, abdominal distention relief time, abdominal pain relief time, length of intensive care unit stay, length of hospital stay, inpatient hospital costs, incidence of complications, and mortality. RESULTS There were significant differences in interleukin-6 and procalcitonin levels and APACHE-II scores after 3 and 7 days of treatment. The duration of systemic inflammatory response, abdominal distention relief time, abdominal pain relief time, length of intensive care unit stay, and length of hospital stay were considerably shorter in the combination group than in the CRRT group (P<0.01). Inpatient hospital costs were significantly lower in the combination group than in the CRRT group (P<0.01). However, incidence of complications and mortality showed no significant differences between the 2 groups. CONCLUSIONS CRRT combined with peritoneal lavage is an important adjuvant therapy in the early stages of acute severe acute pancreatitis and has better clinical efficacy than CRRT alone.