Radical antegrade modular pancreatosplenectomy (RAMPS) has been adopted by some surgeons in the treatment of left-sided pancreatic cancer (PDAC). Low disease incidence and heterogenous disease biology make robust prospective comparison of RAMPS and standard distal pancreatosplenectomy (DPS) difficult.Consecutive cases of chemo-naïve patients undergoing open RAMPS and DPS for PDAC between 2010-2017 at two international high-volume pancreatectomy centers were compared. Cox proportional hazard modeling was utilized for multivariate analysis.We identified 193 DPS and 253 RAMPS during the study period. DPS was associated with higher rates of median estimated blood loss (500 vs. 300 cc, P0.001), median total harvested lymph nodes (18 vs. 12, P0.001) and R0 resection (94.3% vs. 88.9%, P=0.013). There were no differences in rates of postoperative pancreatic fistula (16.5% vs. 17.8%, P=1) or postoperative hemorrhage (5.9% vs. 3.6%, P=0.385) (DPS vs. RAMPS). After controlling for significant clinical pathological parameters, RAMPS was associated with non-superior recurrence-free survival (RFS) (HR 0.29; 95% CI, 0.07-1.27, P=0.101) and overall-survival (HR 1.03; 95% CI, 0.71-1.49, P=0.895) compared with DPS. Similar results were observed in node-positive patients.RAMPS is safe and effective in the treatment of PDAC, but is not associated with an improvement in either RFS or overall-survival over DPS.