Background Both metoprolol and carvedilol improve cardiac function and prolong survival in patients with heart failure. Carvedilol has broader antiadrenergic effects than metoprolol, but it is not clear whether this characteristic is associated with greater benefits on cardiac function during long-term treatment. Study Design We performed a meta-analysis of all 19 randomized controlled trials of carvedilol or metoprolol that measured left ventricular ejection fraction before and after an average of 8.3 ± 0.1 months of treatment in 2184 patients with chronic heart failure. The mean daily doses were 58 ± 1 mg of carvedilol and the equivalent of 162 ± 1 mg of extended-release metoprolol. In the 15 placebo-controlled trials, the mean ejection fraction increased more in the trials of carvedilol than in the trials of metoprolol (placebo-corrected increases of +0.065 and +0.038, respectively), P = .0002. In the 4 active-controlled trials that compared metoprolol directly with carvedilol, the mean ejection fraction also increased more in the carvedilol groups than in the metoprolol groups (+0.084 on carvedilol and +0.057 on metoprolol, respectively), P = .009. The difference in favor of carvedilol in the active-controlled trials was nearly identical to the difference observed in the placebo-controlled trials and was apparent in patients with and without coronary artery disease. Conclusion Long-term treatment with carvedilol produces greater effects on left ventricular ejection fraction than metoprolol when both drugs are prescribed in doses similar to those that have been shown to prolong life. (Am Heart J 2001;141:899-907.)