The study was undertaken to investigate the effect of metoprolol CR/XL on all-cause mortality in patients with heart failure in New York Heart Association (NYHA) class II-IV. In all, 3,991 patients in NYHA class II-IV who were stable on standard medical treatment, including angiotensin-converting enzyme inhibitors, diuretics, and digitalis, were randomized to metoprolol CR/XL or placebo and uptitrated from 12.5 or 25 mg to 200 mg over an 8-week period and were planned to be followed for a period of 2 years. The study was stopped earlier than planned due to the significant benefit achieved with metoprolol CR/XL on all-cause mortality. Treatment with metoprolol CR/XL was associated with a 34% decrease in all-cause mortality, 38% decrease in cardiovascular mortality, 41% decrease in sudden death, and 49% decrease in death due to progressive heart failure. The average dose of metoprolol CR/XL at the end of the study was 159 mg, and 64% of the patients were receiving 200 mg of metoprolol CR/XL. There was no significant difference in the placebo and active treatment group with regard to permanent discontinuation. Treatment of patients in NYHA class II-IV with metoprolol CR/XL is associated with a significant decrease in total mortality.