Abstract Background and purpose Pulmonary homograft stenosis can appear in long-term follow-up after Ross intervention. Our aim was to describe the incidence, clinical impact and predictors of homograft stenosis and reintervention after the Ross procedure in a prospective series in a tertiary referral hospital after 21 years followup. Methods From 1997 to 2009, 107 patients underwent the Ross procedure (mean age: 30 ± 11 years; 69% men; 21 aged <18 years). In all of them, a comprehensive clinical and echocardiographic evaluation was performed before the intervention and at discharge, at 6, 12 months and annually after surgery. We analyzed echocardiographic homograft stenosis (peak gradient > 36 mmHg) and surgical or percutaneous homograft reintervention. Results At the end of follow-up (21 years, median: 17 years, interquartile rank 12-19 years), echocardiographic and clinical data were available in 95 (89%) and 105 (98%) patients, respectively: 28/95 (29%) patients developed homograft stenosis and 13/105 (12%) patients underwent diferent homograft reintervention procedures (five patients underwent surgical replacement, four received a percutaneous pulmonary valve and one needed stent implantation). The other three patients underwent two or even three consecutive procedures in follow-up; two died because of complications after percutaneous pulmonary valve implantation and other one after surgical replacement. Rates of survival free from homograft stenosis and reintervention at the end of the follow-up were 71% and 88%, respectively. Younger age, and especially being part of paediatric group (<18 years) at surgical time predicted worse survival free from homograft stenosis (hazard ratio HR 3.88, 95% confidence interval CI: 1.78-8,43; p = 0.001), although there were no significant differences regarding reintervention (HR 1.54, CI 95% 0.42-5.58, p = 0.52). We found no significant association of this outcome with previous cardiac surgery, donor age, donor or recipient sex, homograft size, time of freezing or congenital aetiology. Conclusions After 21 years follow-up, incidence of homograft stenosis and reintervention after the Ross procedure were 29% and 12%, respectively; three patients had a reintervention-related death. Younger recipient age at Ross procedure was associated with a higher rate of stenosis.