Background: Postoperative low cardiac output syndrome (LCOS) is associated with high morbidity and mortality after coronary artery bypass grafting (CABG). We sought to examine trends in predictors of LCOS after isolated CABG. Methods: A total of 25,176 consecutive patients who underwent isolated CABG between 1990 and 2009 were included. To examine trends over time, we divided patients into four equivalent eras (1990 to -1994, n = 6,489; 1995 to 1999, n = 8,175; 2000 to 2004, n = 6,741; 2005 to 2009, n = 3,797). We used multivariable analysis to identify predictors of LCOS. Results: The prevalence of LCOS declined from 9.1% (1990 to 1994) to 2.4% (2005 to 2009, p < 0.001). The following were the major independent predictors of LCOS for the entire cohort (odds ratios in parentheses): reoperative CABG (4.1); earlier year of operation (4.1, 2.6, 1.7 for the first, second, and third eras, respectively); left ventricular ejection fraction (LVEF) less than 0.20 (3.5), emergency surgery (2.7), cardiogenic shock (2.3), female gender (2), and LVEF 0.20 to 0.39 (2). Unlike other risk factors, the impact of LVEF less than 0.20 on development of postoperative LCOS increased substantially in the latest era (odds ratio, 7.8) compared with (odds ratios, 3.1, 4.3, and 3.2) the first, second, and third eras, respectively. Conclusions: The impact of LVEF less than 0.20 on development of postoperative LCOS has increased markedly in the latest era of our study. Prudent preoperative evaluation in patients with severe left ventricular dysfunction is critical. Further innovative research in myocardial protection and circulatory support is warranted in patients with severe left ventricular dysfunction.