BACKGROUND Acute necrotizing pancreatitis is a severe and life-threatening condition. It poses a considerable challenge for clinicians due to its complex nature and the high risk of complications. Several minimally invasive and open necrosectomy procedures have been developed. Despite advancements in treatment modalities, the optimal timing to perform necrosectomy lacks consensus. AIM To evaluate the impact of necrosectomy timing on patients with pancreatic necrosis in the United States. METHODS A national retrospective cohort study was conducted using the 2016-2019 Nationwide Readmissions Database. Patients with non-elective admissions for pancreatic necrosis were identified. The participants were divided into two groups based on the necrosectomy timing: The early group received intervention within 48 hours, whereas the delayed group underwent the procedure after 48 hours. The various intervention techniques included endoscopic, percutaneous, or surgical necrosectomy. The major outcomes of interest were 30-day readmission rates, healthcare utilization, and inpatient mortality. RESULTS A total of 1309 patients with pancreatic necrosis were included. After propensity score matching, 349 cases treated with early necrosectomy were matched to 375 controls who received delayed intervention. The early cohort had a 30-day readmission rate of 8.6% compared to 4.8% in the delayed cohort (P = 0.040). Early necrosectomy had lower rates of mechanical ventilation (2.9% vs 10.9%, P < 0.001), septic shock (8% vs 19.5%, P < 0.001), and in-hospital mortality (1.1% vs 4.3%, P = 0.01). Patients in the early intervention group incurred lower healthcare costs, with median total charges of $52202 compared to $147418 in the delayed group. Participants in the early cohort also had a relatively shorter median length of stay (6 vs 16 days, P < 0.001). The timing of necrosectomy did not significantly influence the risk of 30-day readmission, with a hazard ratio of 0.56 (95% confidence interval: 0.31-1.02, P = 0.06). CONCLUSION Our findings show that early necrosectomy is associated with better clinical outcomes and lower healthcare costs. Delayed intervention does not significantly alter the risk of 30-day readmission.