Background: Nintedanib is an inhibitor of receptor tyrosine kinases, including vascular endothelial growth factor receptor, but its effects on pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) patients with chronic hypoxia were unclear. Methods: This study included a nintedanib prospective study and historical control study. In the nintedanib prospective study, pulmonary artery systolic pressure (PASP) measured using transthoracic echocardiography was evaluated at six points during 48 weeks in 16 IPF patients in whom nintedanib was started. In the historical control study, adjusted annual change in PASP was between patients treated with (n = 16) and without (n = 15) nintedanib. Results: In the nintedanib prospective study, the mean PASP at 48 weeks after starting nintedanib was significantly higher compared to that at baseline. When IPF patients were divided into two groups, IPF patients with or without long-term oxygen treatment (LTOT), mean PASP at 48 weeks was significantly higher than that at baseline only in IPF patients receiving LTOT (P = 0.001). In the historical control study, adjusted annual change in PASP in IPF patients treated with nintedanib was significantly lower than that in patients treated with no antifibrotic agents when considering patients without LTOT (0.26 mmHg vs 7.05 mmHg; P = 0.011). Conclusions: We found differential effects of nintedanib on PH between IPF patients with or without LTOT. Nintedanib may have a disadvantageous effect on PH in IPF patients with LTOT. Conversely, nintedanib treatment may be beneficial to PH in IPF patients without LTOT.