Background <p>IgG4-related autoimmune pancreatitis (IgG4-AIP) is a rare inflammatory condition of the pancreas that is mediated by autoimmune mechanisms and constitutes the most prevalent manifestation of IgG4-related disease (IgG4-RD). This study aims to analyze and compare the clinical characteristics between patients with pancreatic involvement and those without in the context of IgG4-RD. Furthermore, it seeks to explore the differences in clinical features among IgG4-AIP patients with and without bile duct involvement.</p> Methods <p>A retrospective analysis of clinical data was conducted in this study involving 82 patients with IgG4-RD who were admitted to Yichang Central People’s Hospital between January 2019 and December 2024</p> Results <p>Among the 82 patients with IgG4-RD, 40 (48.78%) patients exhibited pancreatic involvement, while 42 (51.22%) patients had non-pancreatic involvement. The incidence of male patients was higher in the pancreatic involvement group compared to the non-pancreatic involvement group (87.50% vs. 66.67%, <i>P</i> &lt; 0.05). Serum IgG4 levels in patients with IgG4-AIP were significantly elevated compared to those in patients without pancreatic involvement (<i>P</i> &lt; 0.05). IgG4-AIP patients were more likely to exhibit involvement of two or more organs simultaneously, with a greater tendency for bile duct involvement (<i>P</i> &lt; 0.05). In contrast, the incidence of pulmonary or salivary gland involvement was relatively low (<i>P</i> &lt; 0.05). In addition, IgG4-AIP patients with bile duct involvement exhibited significantly higher levels of basophils, eosinophils, alkaline phosphatase (ALP), bilirubin, and erythrocyte sedimentation rate (ESR) compared to those without bile duct involvement (<i>P</i> &lt; 0.05).</p> Conclusions <p>IgG4-AIP presents with more complex clinical characteristics. Clinicians should develop a thorough understanding of these features and formulate individualized diagnostic and therapeutic strategies to improve patient outcomes.</p>