YKL-40, a chitinase-like protein mainly secreted by macrophages, neutrophils and epithelial cells, is increased in patients with idiopathic interstitial pneumonia and sarcoidosis. We aimed to investigate the role of YKL-40 as a biomarker in hypersensitivity pneumonitis (HP).72 HP patients, 100 interstitial lung disease (ILD) controls and 60 healthy controls were studied. YKL-40 was measured by ELISA in serum and bronchoalveolar lavage fluid (BALF) at baseline and follow-up. The relationship between YKL-40 levels, clinical variables and disease outcome was evaluated.Baseline serum YKL-40 levels were significantly higher in HP patients than in healthy controls (p<0.001), but lower than in patients with other ILDs. Baseline BALF YKL-40 levels in HP patients were the highest among ILD patients. In HP patients, serum YKL-40 correlated with the diffusing capacity of the lung for carbon monoxide at baseline (p<0.01) and over time (p<0.001). HP patients whose disease progressed or who died had higher baseline YKL-40 levels than those who remained stable and survived (p<0.001). At a cut-off of 119 ng·mL^-1, the baseline serum YKL-40 level predicted disease progression (hazard ratio 6.567; p<0.001), and at a cut-off of 150 ng·mL^-1 was associated with mortality (hazard ratio 9.989; p<0.001).Serum YKL-40 may be a useful prognostic biomarker in HP patients.