Aim: Recurrent aphthous stomatitis (RAS) is an inflammatory condition of the oral mucosa. The etiology of RAS remains unclear. Calprotectin is a major cytoplasmic protein contained in granulocytes, monocytes/macrophages and epithelial cells, and its level is increased body fluids in some inflammatory diseases. The aim is to determine the relationship between salivary calprotectin and RAS. Material and Methods: In the cross-sectional study, 67 patients with active lesions of RAS (F/M: 43/24, mean age: 30.27 +/- 9.14 years) and 42 healthy controls (HC, F/M: 30/12, 30.54 +/- 9.49 years) were included. Calprotectin levels were evaluated in unstimulated whole saliva samples by using the ELISA method in both groups. Results: Salivary calprotectin levels were significantly higher in RAS group (23.72 +/- 4.28 mg/L) compared to the HC group (21.59 +/- 4.27 mg/L) (P = 0.013). No significant relationship was found between calprotectin levels and age or gender in both groups (P > 0.05). Conclusion: RAS is a very common inflammatory ulcerative condition of the oral cavity and its etiology is uncertain. Regarded as an inflammatory mechanism, releasing a high level of calprotectin in saliva has been suggested that it may play a role in pathogenesis of RAS.