Background: The Mosaic bioprosthesis is a third-generation stented porcine bioprosthesis combining physiologic fixation and alpha-amino oleic acid (AOA) antimineralisation treatment to improve haemodynamic performance and durability. This single-centre study reports the clinical results, including haemodynamic performance, of the Mosaic bioprosthesis after implant in aortic or mitral position. Methods: Between February 1994 and October 1999, 255 patients with aortic valve replacement (AVR; mean age: 67 years, range: 23–82 years) and 47 patients with mitral valve replacement (MVR; mean age: 67 years, range: 41–84 years) were enrolled in this prospective non-randomised clinical trial. Follow-up visits were performed 30 days and 6 months after implant and annually thereafter. The cumulative follow-up was 1976.2 patient-years (pt-yrs) after AVR (median: 8.3 years, maximum: 14.0 years) and 336.9 pt-yrs after mitral valve replacement (MVR) (median: 8.2 years, maximum: 13.3 years). Results: After AVR, mean systolic gradient and effective orifice area at 4, 8 and 13 years follow-up were 13.3±5.6, 15.5±7.7 and 16.0±7.2mmHg and 1.8±0.5, 1.8±0.5 and 1.7±0.4cm 2 . After MVR, respective data were 4.7±2.1, 4.3±1.2 and 5.0mmHg (only one recording) and 2.2±0.7, 2.3±0.6 and 1.8cm 2 . Transvalvular regurgitation at 13-year follow-up was mild or less in both the AVR and MVR patients. Thirteen-year survival was 63.1±4.5% in the AVR group and 51.2±13.6% in the MVR group. Early mortality after AVR and MVR was 1.2% and 0.0%, respectively; late mortality was 3.2%pt-yr −1 and 3.3%pt-yr −1 , including a valve-related/unexplained mortality of 1.1%pt-yr −1 and 0.9%pt-yr −1 . Freedom from adverse events in the AVR and MVR group was permanent neurological event: 97.4±1.2% and 96.0±3.9%; valvular thrombosis: 97.8±1.1% and 100%; structural valve deterioration: 84.8±7.8% and 93.8±6.1%; explant: 73.3±7.3% and 89.3±6.5%. Conclusions: The Mosaic bioprosthesis demonstrates excellent clinical performance and safety after 13 years of follow-up. Continued follow-up will determine whether this new design will provide increased durability.