Introduction: Accumulating evidence suggests that enhanced external counterpulsation (EECP) influences cardiac functions, hemodynamic characteristics and cerebral blood flow. However, little is known about whether or how the EECP affects the brain-heart coupling to produce these physiological and functional changes. We aimed to determine if the brain-heart coupling is altered during or after EECP intervention by assessing the heartbeat evoked potential (HEP) in healthy adults.Methods: Based on a random sham-controlled design, simultaneous electroencephalography and electrocardiography signals as well as blood pressure and flow status data were recorded before, during and after two consecutive 30-min EECP in 40 healthy adults (female/male: 17/23; age: 23.1 ± 2.3 years). HEP amplitude, frequency domain heart rate variability, electroencephalographic power and hemodynamic measurements of 21 subjects (female/male: 10/11; age: 22.7 ± 2.1 years) receiving active EECP were calculated and compared with those of 19 sham control subjects (female/male: 7/12; age: 23.6 ± 2.5 years).Results: EECP intervention caused immediate obvious fluctuations of HEP from 100 to 400 ms after T-peak and increased HEP amplitudes in the (155–169) ms, (354–389) ms and (367–387) ms time windows after T-peak in the region of the frontal pole lobe. The modifications in HEP amplitude were not associated with changes in the analyzed significant physiological measurements and hemodynamic variables.Discussion: Our study provides evidence that the HEP is modulated by immediate EECP stimuli. We speculate that the increased HEP induced by EECP may be a marker of enhanced brain-heart coupling. HEP may serve as a candidate biomarker for the effects and responsiveness to EECP.