Abstract Background Percutaneous transluminal pulmonary venoplasty (PTPV) is an emerging treatment for pulmonary vein stenosis caused by fibrosing mediastinitis (PVS-FM). However, the incidence and predictors of in-stent restenosis (ISR) are elusive. Purpose We aim to identify the incidence and predictors of ISR in patients with pulmonary vein stenosis (PVS) caused by extra-luminal compression due to fibrosing mediastinitis (FM). Methods We enrolled patients with PVS-FM who underwent PTPV between 2018 and 2022. Patients were divided into ISR and non-ISR groups based on the presence of ISR. Baseline characteristics (demographics and lesions) and procedure-related information were abstracted from patient records and analyzed. Univariate and multivariate analyses were performed to determine the predictors of ISR. Results A total of 109 stents were implanted in 102 PVs of 50 patients with PVS-FM. Over a median follow-up of 4.0 months (interquartile range: 3.0 to 11.0 months), there were 47 of 102 PVs suffered from ISR. The cumulative ISR was 3%, 12%, 42%, and 50% at 1-, 3-, 6-, and 12-month follow-up, respectively. Multivariate analysis demonstrated a significantly lower risk of ISR in PVs with a larger reference vessel diameter (RVD) (OR 0.64, 95%CI 0.48-0.86, p = 0.002) and the narrowing severity of the corresponding pulmonary artery (Cor-PA) (severe) independently increased the risk of ISR (OR 6.63, 95%CI 1.82-24.18, p = 0.004), respectively. Conclusions ISR is very high in PVS-FM, which is independently associated with Cor-PA stenosis and RVD.