The purpose of this study was to examine the usefulness of ¹¹C-acetate positron emission tomography (PET) for assessing the efficacy of cardiac resynchronization therapy (CRT). Enrolled in this study were 20 patients with severe heart failure. All patients underwent 11C-acetate PET within 1 week after CRT. The oxygen consumption was measured by the monoexponential clearance rate of 11C-acetate (K_mono) for both CRT-off and -on. Cardiac efficiency (CE) was determined using the concept of the work metabolic index (WMI). WMI was calculated as WMI = (stroke volume index) × (systolic blood pressure) × (heart rate)/K_mono. The patients were divided into two groups: 14 patients with improved CE (from 5.27 ± 0.91 to 6.77 ± 1.12) and 6 patients with deteriorated CE (from 5.35 ± 0.92 to 4.86 ± 0.84) by CRT-on. K_mono decreased from 0.053 ± 0.006 to 0.046 ± 0.003 by CRT-on in the improved CE group (p = 0.028), but increased from 0.049 ± 0.006 to 0.050 ± 0.006 in the deteriorated-CE group (p = 0.036). Stroke volume index, systolic blood pressure, and heart rate did not change by CRT-on for either group. At the one-year follow-up, there were significantly higher rates of major cardiac adverse events in the deteriorated-CE group than in the improved-CE group (p = 0.032). Therefore, the improvement of CE, as assessed by 11C-acetate PET in the early period after CRT, is produced by the decrease in oxygen consumption in patients showing good responses to CRT. The decrease in oxygen consumption in the early period after CRT is thus a useful marker for predicting a good clinical outcome after CRT.