Background: Evidence suggests externalized trans-anastomotic stents may be beneficial as a fistula mitigation strategy for pancreatoduodenectomy (PD); however, previous studies have not been rigorously risk-adjusted. Methods: From 2001 to 2015, PDs were performed at three institutions, with externalized stents placed at the surgeon’s discretion. The Fistula Risk Score (FRS) and the Modified Accordion Severity Grading System were used to analyze occurrence and severity of clinically relevant postoperative pancreatic fistula (CR-POPF) across various risk scenarios. Results: Of 729 PDs, externalized stents were placed during 129 (17.7 %). Overall, CR-POPFs occurred in 77 (10.6 %) patients. The median FRS of patients who received externalized stents was significantly higher compared with patients who did not (6 vs. 3, p < 0.0001). Patients with negligible, low, or moderate CR-POPF risk (FRS 0–6) did not demonstrate improved outcomes with externalized stents; however, among high-risk patients (FRS 7–10), stents were associated with significantly reduced rates of CR-POPF (14.0 vs. 36.4 %, p = 0.031), severe complications (p = 0.039), and hospital stay (p = 0.014) compared with no stents. The average complication burden of CR-POPF was significantly lower for patients with externalized stents (p = 0.035). Conclusion: This multicenter study, the largest comparative analysis of externalized trans-anastomotic stents versus no stent for PD, demonstrates a risk-stratified benefit to externalized stents.