Objectives: Immunoglobulin G4 (IgG4)-related sclerosing disease may manifest as cardiovascular disorders, such as inflammatory abdominal aortic aneurysm and lymphoplasmacytic aortitis. Immune inflammatory process is recognized to underlie the pathogenesis of atherosclerosis, thus we investigated the serum levels of IgG4. Methods: Serum levels of IgG4 and soluble interleukin-2 receptor (sIL-2R), another marker for lymphocytic activation, were measured in 571 patients (424 males) who underwent coronary angiography. Among the 571 patients enrolled, 409 patients had angiographically-proven coronary artery disease (CAD). In addition, 86 patients had aortic aneurysm: abdominal aortic aneurysm alone, 49; thoracic aortic aneurysm alone, 21, and both abdominal and thoracic aortic aneurysm, 16. Results: The mean age of the 571 patients was 66.9 ± 10.3 years. In patients with CAD, the medians of serum levels of IgG4 (34.1 mg/dL) and sIL-2R (396 U/mL) were significantly higher than in those without CAD (IgG4, 30.5 mg/dL, P=0.045; sIL-2R, 322 U/mL, P<0.001). Age and gender-adjusted logistic regression analysis showed that the first (151-292 U/mL), second (293-378 U/mL), third (379-509 U/mL), and fourth (510-3180 U/mL) quartiles of sIL-2R levels had the graded association with CAD with the odds ratio of 1 (reference), 2.21 (95% CI 1.32-3.71), 2.25 (95% CI 1.32-3.85), and 2.50 (95% CI 1.45-4.30), respectively. The fourth quartiles of IgG4 (≥ 57.1 mg/dL) and sIL-2R (≥ 510 U/mL) were also predictive of CAD with an odds ratio of 2.21 and 2.13, respectively, compared with the lowest quartiles among 371 subjects without PCI/CABG history. The medians of IgG4 and sIL-2R levels in patients with aortic aneurysm were 36.6 mg/dL and 384 U/mL, respectively, and these did not significantly differ from those without aortic aneurysm (IgG4, 32.5 mg/dL; sIL-2R, 374 U/mL). Conclusions: Serum levels of IgG4, as well as sIL-2R, were significantly higher in patients with CAD than in those without CAD among subjects without previous coronary interventions, suggesting that IgG4-related immune inflammation may play a role in the coronary atherogenesis. On the other hand, values of these markers did not significantly differ according to the presence or absence of the aortic aneurysm.