Objective The study's objectives were to evaluate results and identify predictors of hospital and mid-term mortality after primary isolated aortic valve replacement; compare early and mid-term survival of patients aged more than 80 years or less than 80 years; and assess the effectiveness of the logistic European System for Cardiac Operative Risk Evaluation in predicting the risk for hospital mortality in octogenarians with a logistic European System for Cardiac Operative Risk Evaluation greater than 15% who are undergoing aortic valve replacement. Methods Data from 2256 patients undergoing primary isolated aortic valve replacement between January 2003 and December 2007 were prospectively collected in a Regional Registry (Regione Emilia Romagna Interventi Cardiochirurgia) and analyzed to estimate hospital and mid-term results. Results Overall hospital mortality was 2.2%. By multivariate analysis, New York Heart Association III and IV, Canadian Cardiovascular Society III and IV, pulmonary artery pressure greater than 60 mm Hg, dialysis, central neurologic dysfunction, and severe chronic obstructive pulmonary disease emerged as independent predictors of hospital mortality. At 3 years, the survival was 89.3%. The same predictors of hospital mortality plus ejection fraction of 30% to 50% and age more than 80 years emerged as independent risk factors for 3-year mortality. Compared with younger patients, octogenarians had a higher hospital mortality rate (3.72% vs 1.81%; P = . 0143) and a reduced 3-year survival (82.3% vs 91.3%; P < . 001). Three-year survival of octogenarians was comparable to the expected survival of an age- and gender-matched regional population ( P = . 157). The observed mortality rate in octogenarians with a logistic European System for Cardiac Operative Risk Evaluation greater than 15% (mean: 22.4%) was 7% ( P < . 001). Conclusions This study provides contemporary data on the characteristics and outcome of patients undergoing first-time isolated aortic valve replacement.