CoolCuddle, enabling parents to cuddle their babies with neonatal encephalopathy (NE) during therapeutic hypothermia and intensive care (TH), was developed in research settings. To determine the impact of implementing CoolCuddle in usual care in six diverse neonatal intensive care units on the cooling process and intensive care. This vital sign cohort study embedded within the CoolCuddle implementation study enrolled 36 infants receiving TH for NE. Nurses received training on CoolCuddle and a standard operating procedure using an instruction video. After consenting, parents experienced up to 2 h of CoolCuddle with 30 min of pre- and post-cuddle observation. We used multilevel, clustered linear modelling to assess the physiological stability in temperature, cardio-respiratory and neurophysiology across the CoolCuddle. In 60 CoolCuddles over 93.12 h, respiratory parameters, heart rate or neurological function did not vary between the epochs (p > 0.05). During cuddle, sleep-wake cycling on amplitude-integrated EEG increased (p = 0.008) and there was weak evidence of lower pain scores (p = 0.08). No adverse effects were observed. Implementing CoolCuddle with support in usual practice maintained physiological stability and did not significantly affect the cooling process or intensive care, and may improve infant comfort. Ongoing monitoring of adverse effects when implementing CoolCuddle is recommended.