Abstract Disclosure: Y. Kim: None. H. Kim: None. M. Yu: None. C. Nam: None. E. Kang: None. Background: Despite diabetes mellitus and pancreatitis being known risk factors for pancreatic cancer, but because of their low incidence, patients with these conditions are not included in pancreatic cancer screening. This study aimed to determine the high-risk subgroup of patients with diabetes and pancreatitis that would benefit from pancreatic cancer screening. Methods: A nested case-control study was conducted using data from the national health information database of the Korean National Health Insurance Service. Patients were categorized into the following groups: type 2 diabetes only (T2D-only), pancreatitis only (PAN-only), type 2 diabetes followed by pancreatitis (T2D-PAN), post-pancreatitis DM (PPDM), and no diabetes and no pancreatitis (NDNP). Conditional logistic regression was used to determine significant associations of each group with pancreatic cancer development risk. Results: The risk of pancreatic cancer was significantly higher in the T2D-PAN (adjusted odds ratio [AOR], 4.96; 95% confidence interval [CI], 4.48-5.49) and PPDM (AOR, 4.71; 95% CI, 4.12-5.37) groups than in the NDNP group. Furthermore, the T2D-PAN and PPDM groups had a significantly higher risk of pancreatic cancer than the T2D-only and PAN-only groups. Compared to patients in the NDNP group, patients with PPDM using insulin had a 9-fold increased risk (AOR, 9.84; 95% CI, 6.77-14.29), and patients with T2D-PAN using insulin had a 6-fold increased risk (AOR, 6.62; 95% CI, 5.33-8.20). Conclusion: Patients with both diabetes and pancreatitis had a higher risk of pancreatic cancer than those with either alone, regardless of the order of occurrence, and insulin use was associated with an additional increase in pancreatic cancer risk. These results suggest that these subgroups of patients could be considered to benefit from pancreatic cancer screening. Presentation: 6/2/2024