The present study was designed to test the hypothesis that low-ejection fraction (EF), low-gradient aortic stenosis (AS) is a predictor of major morbidity after aortic valve replacement (AVR). We retrospectively analyzed prospectively collected data from 597 consecutive patients with AS (mean age 72 +/- 11 years) who had undergone AVR or combined AVR and coronary artery bypass grafting (CABG) from 1998 to 2006 (EF < or =30% in 73 [12%]). The outcome measures included hospital mortality, major complications, and long-term survival. The overall hospital mortality rate was 4% (low-EF AS 5%; low-EF AS plus CABG 8%; AS controls 4%; AS plus CABG controls 3%; p = 0.42). Low-EF, low-gradient AS was not an independent risk factor for hospital mortality but predicted stroke (odds ratio [OR] 4.3), deep sternal wound infection (OR 10.0), sepsis (OR 6.8), gastrointestinal complications (OR 4.2), and respiratory failure (OR 4.4). The survival rate at 1, 3, and 5 years was 69 +/- 8%, 69 +/- 8%, and 65 +/- 8% in the low-EF, low-gradient, AVR plus CABG group and 95 +/- 4%, 92 +/- 5%, and 82 +/- 7% in the low-EF, low-gradient AVR group compared to 93 +/- 2%, 88 +/- 2%, and 78 +/- 3% in the AVR plus CABG control group and 93 +/- 2%, 89 +/- 2%, and 85 +/- 3% in the AVR control group (p = 0.001), respectively. In the patients with low-EF AS who experienced major postoperative morbidity, the 1-year survival rate was significantly reduced (54 +/- 14%) compared to those who did not (95 +/- 3%, p <0.001). In conclusion, low-EF, low-gradient AS is a predictor of increased major morbidity after AVR, which nonetheless remains the treatment of choice for most patients because of the excellent early and late survival. However, patients with strong risk factors for postoperative renal and respiratory failure might derive less benefit from conventional surgical AVR.