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Background: Hyperlipidaemic acute pancreatitis (HLAP) has become the most common cause of acute pancreatitis (AP) not due to gallstones or alcohol (Mosztbacher et al, Pancreatology 20:608-616, 2020; Yin et al, Pancreas 46:504-509, 2017). Therapeutic plasma exchange (TPE) has been reported to be effective in reducing serum TG levels which is important in management of HLAP (World J Clin Cases 9:5794-803, 2021). However, studies on TPE are mostly focusing on cases reports, TPE remains poorly evaluated till date and need to be compared with conservative therapy with a well-designed study. Methods: A retrospectively cohort study on HLAP patients between January 2003 and July 2023 was conducted. Factors correlated with efficacy of TPE were included in a propensity model to balance the confounding factors and minimize selection bias. Patients with and without TPE were matched 1:2 based on the propensity score to generate the compared groups. Lipid profiles were detected on admission and consecutive 7 days. The triglyceride (TG) level decline rates, percentage of patients to reach the target TG levels, early recurrence rate, local complications and mortality were compared between groups. Results: A total of 504 HLAP patients were identified. Since TPE was scarcely performed on patients with TG < 11.3 mmol/L, 152 patients with TG level 5.65 to 11.3 mmol/L were excluded while 352 with TG ≧11.3 mmol/L were enrolled. After excluding 25 cases with incomplete data or pregnancy, 327 patients, of whom 109 treated without TPE while 218 treated with TPE, were included in data analysis. One-to-two propensity-score matching generated 78 pairs, 194 patients with well-balanced baseline characteristics. Of 194 patients enrolled after matching done, 78 were treated without while 116 with TPE. In the matched cohort (n = 194), patients treated with TPE had a higher TG decline rate in 48 h than those without TPE (70.00% vs 54.00%, P = 0.001); the early recurrence rates were 8.96% vs 1.83%, p = 0.055. If only SAP patients were analyzed, the early recurrence rates were 14.81% vs 0.00% (p = 0.026) respectively. For patients with CT severity index (CTSI) rechecked within 14 days, early CTSI improment rate were 40.90% vs 31.91%. Local complications checked 6 months after discharge were 44.12% vs 38.30%. Mortality was 1.28% vs 1.72%. No differences were found in early stage CTSI improment rate (P =.589), local complications (P =.451) or motality between two groups. Conclusions: TPE reduces TG levels more quickly in 48 h compared with those with conservative treatment, but no difference in the consecutive days. TPE tends to reduce the early recurrence rate comparing with conventional therapy, but TPE has no advantages in improving CTSI in early stage, and no improvement for outcomes including local complications and mortalty. [ABSTRACT FROM AUTHOR]