Purpose. High lactate levels at hospital admission are significantly associated with poor prognosis in acute pancreatitis patients. Early high lactate clearance is a vital marker for predicting persistent organ failure and mortality in critical illness; however, its value in acute pancreatitis remains unclear. Method. Data were collected from patients who were diagnosed with moderately severe acute pancreatitis and severe acute pancreatitis from January 2017 to December 2020. Initial lactate (within 2 hours after admission) and repeat lactate at 24 hours after admission were measured to determine lactate clearance. Low clearance was defined as a reduction in repeat lactate of less than 30% compared to the first measurement. High clearance was defined as a repeat lactate decrease ≥30% of the first measurement or both first and second lactate levels <2 mmol/L. Baseline data, laboratory data, mortality rate, persistent organ failure rate, and other outcomes such as the incidence of septic pancreatic necrosis and sepsis and the length of hospital stay and intensive care unit (ICU) stay were compared in the low and high lactate clearance groups. Multivariate logistic regression analyses were used to assess the value of lactate clearance for predicting death. Result. Among 4425 acute pancreatitis patients, 3040 patients were diagnosed with moderate or severe acute pancreatitis, and 1028 patients had initial lactate measured. Finally, 390 patients who had initial and 24-hour repeat lactate data were included in the study. Patients who had elevated initial lactate had poor outcomes, and 51 patients in the initial elevated lactate group died. In the lactate normalization group analysis, 293 patients had 24-hour lactate normalization; compared with patients in the nonnormalization group, they had a lower rate of mortality (12.6% vs. 33%). In the lactate clearance group analysis, 70 (21.9%) patients had a low clearance after 24 hours; compared with patients in the high clearance group, they had a higher rate of developing persistent multiorgan failure ( P = 0.045 ), and the incidence of death was higher (15% vs. 28.6%, P = 0.007 ). Multivariate logistic analysis showed that 24-hour lactate clearance (OR: 2.007; 95% CI:1.032-3.903, P = 0.04 ), elevated initial lactate (OR: 2.011; 95% CI:1.023-3.953, P = 0.043 ), blood urea nitrogen (OR: 2.316; 95% CI:1.061-5.056, P = 0.035 ), and white blood count (OR: 1.982; 95% CI:1.026-3.829, P = 0.042 ) were independent predictors of hospital mortality. Conclusion. The 24-hour clearance of lactate is a reliable marker to predict the outcome of moderate and severe acute pancreatitis, and low lactate clearance may indicate that the patient’s condition will worsen, requiring aggressive treatments to improve patient outcomes.