A recent preclinical study suggested that imatinib may be cardiotoxic in some patients. We reviewed all reported serious adverse events of cardiac adverse events occurring in patients on clinical trials involving imatinib. Among 1276 patients enrolled, 22 (1.7%) were identified as having symptoms that could be attributed to systolic heart failure. The median age was 70 years (range, 49 to 83 years). The median time from start of imatinib therapy was 162 days (range, 2-2045 days). At the time these events were reported, 8 (0.6%) were considered possibly or probably related to imatinib. A total of 18 patients had previous medical conditions predisposing to cardiac failure: congestive heart failure (CHF; 6 [27%] patients), diabetes mellitus (6 [27%] patients), hypertension (10 [45%] patients), coronary artery disease (CAD; 8 [36%] patients), arrhythmia (3 [14%] patients), and cardiomyopathy (1 [5%] patient). Of the 22 patients, 11 continued imatinib therapy with dose adjustments and management for the CHF symptoms without further complications. Imatinib therapy as a causal factor of CHF is uncommon, mainly seen in elderly patients with preexisting cardiac conditions. Patients with previous cardiac history should be monitored closely and treated aggressively with standard medical therapy, including diuretics, if they develop symptoms suggestive of heart failure.