© 2019 Elsevier Ltd Background: and purpose: Heart rate variability (HRV) represents a marker of autonomic activity, self-regulation and psychiatric illness. Few studies of manual therapy have investigated the neurophysiological effects of manual cranial therapy (MC-t). This study assessed the neurophysiological short/medium-term effects of two manual therapy interventions: massage therapy (Mss-t) and MC-t. Materials and methods: A double-blind clinical trial was conducted with 50 healthy children, randomized into two groups who received a Mss-t intervention or MC-t. The variables analysed included vital signs (temperature, respiratory rate, heart rate, blood pressure) and HRV components, including the root mean square of successive differences (RMSSD), high frequency (HF), low frequency (LF) and LF/HF ratio. Results: Both interventions produced short-term parasympathetic effects, although the effects of MC-t were more persistent. Conclusion: The persistence of the MC-t intervention suggested a prominent vagal control and better self-regulation. Autonomic imbalances in mental pathologies may benefit from the neurophysiological effects of MC-t.