Background To evaluate a risk‐adjusted comparison of clinically relevant postoperative pancreatic fistula POPF (CR‐POPF) following laparoscopic pancreatoduodenectomy (LPD) vs open pancreatoduodenectomy (OPD) using the fistula risk score (FRS). Methods We retrospectively analyzed 579 patients who underwent LPD (n = 274) or OPD (n = 305) between 2012 and 2019 at two tertiary hospitals. Using the FRS, the risk was stratified into four categories; negligible, low, intermediate and high risk. Results The median FRS was significantly higher in the LPD than in the OPD group (5.4 ± 1.2 vs 3.9 ± 1.8, P < .001). The overall incidence of CR‐POPF in the LPD vs OPD groups were 16.4% vs 17.7% (P = .187). When POPF risks were stratified by FRS, CR‐POPF following LPD vs OPD in patients with low risk (0% vs 6.3%, P = .294), intermediate risk (16.1% vs 22.9%, P = .053) and high risk (33.3% vs 27.3%, P = .577) were not significantly different. Conclusion Despite a higher risk score in the LPD group, the CR‐POPF was similar following both procedures in the unadjusted and FRS‐risk‐adjusted comparisons. The CR‐POPF was more significantly affected by patient risk factors such as the soft pancreas and small pancreatic duct. Highlight Lee and colleagues conducted a risk‐adjusted comparison of clinically‐relevant postoperative pancreatic fistula following laparoscopic pancreatoduodenectomy versus open pancreatoduodenectomy using the fistula risk score system. The incidence of clinically‐relevant postoperative pancreatic fistula was similar following the two procedures, in both the unadjusted as well as the fistula risk score‐adjusted comparisons.