Idiopathic pulmonary fibrosis is a fibrotic disease of unknown aetiology and has a poor prognosis. Some patients experience episodes of rapid deterioration known as acute exacerbations (AEs), which are often fatal. This study aimed to clarify whether serum cytokine levels can predict the outcome of idiopathic pulmonary fibrosis. This retrospective study included 69 patients with idiopathic pulmonary fibrosis diagnosed according to the 2018 guideline. AE of idiopathic pulmonary fibrosis was diagnosed using the Japanese Respiratory Society criteria. Serum levels of 27 cytokines were measured using the Bio-Plex method. Cytokine production was estimated per lung volume using the serum cytokine level/percent predicted forced vital capacity (%FVC) value. The ability of the serum cytokine level and serum cytokine level/%FVC value to predict the prognosis and AE was examined in a univariate Cox proportional hazards regression model; significant factors were subjected to multivariate analysis with adjustment for significant clinical parameters, including the modified Medical Research Council score. The study included 57 men and 12 women (median age, 67 years). The modified Medical Research Council score was ≤1 in 47 patients and ≥2 in 22. None of the serum cytokine levels measured could predict survival or AE; however, the serum platelet-derived growth factor/%FVC and interleukin-9/%FVC values were significant prognostic factors and the serum platelet-derived growth factor/%FVC and interleukin-13/%FVC values were significant predictors of AE. Serum platelet-derived growth factor/%FVC alone was a significant predictor of the prognosis and AE after adjustment for clinical parameters. The prognosis of idiopathic pulmonary fibrosis and AEs of the disease could be predicted by the serum platelet-derived growth factor/%FVC value.