The long-term (18 years) outcome of 279 Hancock II bioprosthesis implantation was investigated after aortic (AVR), mitral (MVR) and double (aortic/mitral, DVR) valve replacement. Follow up was 96% complete (total 1,857 patient-years). Actuarial survival at 18 years was 44.7 ± 8.8% after AVR and 32.7 ± 11.5% after MVR; survival after DVR was 74.0 ± 11.2% at 12 years. Freedom from structural deterioration at 18 years was 18.7 ± 14.6% after AVR and 32.1 ± 10.2% after MVR; at 12 years after DVR it was 32.0 ± 24.2%. A low incidence of structural valve deterioration was found in AVR patients aged >65 years (p = 0.0478). In conclusion, over an 18-year follow up, the Hancock II bioprosthesis has shown satisfactory results, with a low incidence of valve-related complications, especially in elderly patients and in the aortic position.