The mortality benefit of implantable cardioverter defibrillator (ICD) therapy in primary and secondary prevention has been shown in various studies in patients with depressed left ventricular systolic function. This study determined the association between the mortality benefit of ICD therapy and the use of β-blocking medication in randomized ICD trials. Eligible studies were randomized controlled trials of ICD therapy compared with conventional medical treatment reporting mortality as an outcome (Medline from May 1995 to May 2005). Ten randomized trials were included. Included studies were reviewed to determine the number of patients, follow-up, and the mortality of ICD and control groups. The analysis of these trials showed a strong negative association between the use of β-blocking medication and the 2-year mortality benefit of ICD therapy (r = −0.81, p <0.01). In conclusion, the use of β-blocking medication is associated with a reduced absolute mortality benefit of ICD therapy in reported randomized trials.