Background <p>IgG4-related autoimmune pancreatitis (IgG4-AIP) is a rare inflammatory pancreatic disorder mediated by autoimmune mechanisms, primarily characterized by two forms of presentation: diffuse enlargement and focal enlargement. This study aims to analyze the clinical characteristics of diffuse and focal enlargement in IgG4-AIP, thereby enhancing clinicians' understanding of the differences between these two patient groups and ultimately improving patient outcomes.</p> Methods <p>This study conducted a retrospective analysis of the clinical data from 40 patients with IgG4-AIP admitted to Yichang Central People's Hospital between January 2019 and December 2024.</p> Results <p>Among the 40 patients with IgG4-AIP, 23 (57.50%) presented with diffuse pancreatic enlargement, while 17 (42.50%) exhibited focal pancreatic enlargement. In the diffuse enlargement group, the most common clinical symptom was abdominal pain (13/23 patients, 56.52%), whereas the focal enlargement group predominantly presented with jaundice (11/17 patients, 64.71%). Additionally, patients in the focal enlargement group were more likely to be misdiagnosed as pancreatic tumors (47.06% vs. 13.04%, <i>P</i> &lt; 0.05). In the focal enlargement group, serum levels of gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were significantly elevated compared to the diffuse enlargement group, while serum albumin (ALB) levels were markedly reduced (<i>P</i> &lt; 0.05). The incidence of pancreatic dilatation was significantly higher in the focal enlargement group compared to the diffuse enlargement group (47.06% vs. 13.04%, <i>P</i> &lt; 0.05).</p> Conclusions <p>The clinical features of focal enlargement in IgG4-AIP are notably more complex. Clinicians should conduct a thorough analysis of the two presentation forms to develop personalized treatment strategies, thereby improving the prognosis for patients with different manifestations of IgG4-AIP.</p>