Background: MUC5AC is a gel-forming glycoprotein that exists in two major glycoforms in PDA. We studied the differential expression and predictive value of heavily glycosylated mature MUC5AC (MM) detected in the apical (Ap) and/or extracellular region (EC) and less-glycosylated immature MUC5AC (IM) detected only in the cytoplasm (Cy) in R-PDA. Methods: R-PDA formalin-fixed paraffin-embedded tissue blocks from January 2010 to June 2021 were obtained from the Ohio State University biorepository. Immunohistochemistry was performed to study the expression for MM and IM using monoclonal antibodies 45M1 and CLH2, respectively, and H-scores were calculated. Analysis of variance (ANOVA), t-tests, and Wilcoxon tests were used for statistical analysis. Results: Tissue samples from 100 R-PDA (43 received NAT and 57 had upfront surgery (UpS)) were available for testing. The median age of diagnosis was 65 years, and 50% were females. MM and IM were positive in 96% R-PDA (MM-95% Ap and 72% EC).In the NAT group, 89% (n=38) had 5-fluorouracil (5FU) based (36 FOLFIRINOX and 2 FOLFOX), and the rest received gemcitabine (Gem)-based therapy; patients received a median of 6 cycles of NAT; 37% (16) had preoperative chemoradiation (CRT) after NAT; 63% (27) had adjuvant systemic therapy (AST); pathologic objective response (OR = near complete or partial) and no response (NR) to NAT was reported in 63% (27) and 37% (16), respectively. In UpS group, 92% and 4% had AST (48 Gem-based, 4 5FU-based) and adjuvant CRT, respectively. The median time to recurrence (mTTR) and overall survival of the group was 15 and 33 months (m), respectively. NAT group had significantly (p<0.05) lower EC-positive MM (mean H-score 108 vs. 151), IM (mean H-score 122 vs. 162), and mTTR (11 vs 15 m) than UpS group. IM levels were directly proportional to the response (near complete (mean H-score 98) < partial (105) < NR (152) < UpS (162), p=0.04). Other TR results are discussed in the table. Conclusions: MUC5AC (IM > MM) is a potential predictive marker for TR among PDA patients, specifically among those receiving FOLFIRINOX. These associations must be validated in further prospective studies.