Background <p>Pancreatic head-type autoimmune pancreatitis (PH-AIP) with elevated CA19-9 is sometimes difficult to distinguish from pancreatic head cancer (PHC) with elevated CA19-9. At times, IgG4 proves inadequate in offering assistance. The study aimed to elucidate the performance of CA19-9/DBil in distinguishing between the two conditions.</p> Methods <p>This was a retrospective study. We collected serologic indicators from participants in PH-AIP and PHC Group. Three logistic regression equations were established ranging from non-adjustment (Model 1, only CA19-9/DBil included) to adjusting for sex, age, and CEA (Model 2 and Model 3) to explore the relationship between CA19-9/DBil and PH-AIP probability. ROC, Decision Curve Analysis (DCA), calibration curve were conducted. <i>P</i> for AUCs and net reclassification improvements (NRI) were computed to evaluate differences in discrimination and the improvement in risk reclassification between models.</p> Results <p>The study included 90 PHC and 35 PH-AIP patients, all with elevated CA19-9. The ORs for CA19-9/DBil in three models were similar (0.915 to 0.921). ROC revealed that Model 1 had an AUC of 0.772. The sensitivity, specificity, and accuracy at the best threshold were all &gt; 0.7. Model 1, although simple, was not inferior in its discriminative ability compared to complex models: the difference in discrimination between Model 1 and each of two adjusted models was not statistically significant (<i>P</i> &gt; 0.05, both AUC and NRI). Additionally, calibration curve and DCA suggested that Model 1 had good calibration and clinical utility.</p> Conclusions <p>CA19-9/DBil exhibited promising diagnostic performance in differentiating between CA19-9-elevated PH-AIP and PHC.</p>