In neonatology, the accurate determination of vital parameters plays a pivotal role in monitoring critically ill newborns and premature infants, as well as aiding in disease diagnosis. In response to the limitations associated with contact-based measurement methods, substantial efforts have been directed toward developing contactless measurement techniques, particularly over the past decade. Building upon the insights gained from our pilot study, we realized a new investigation to assess the precision of our imaging photoplethysmography-based system within a clinical environment of the neonatal intermediate care unit. We conducted measurements in 20 preterm infants or newborns requiring therapeutic interventions. As a point of reference, we employed a conventional pulse oximeter. To analytically predict measurement artifacts, we analyzed the potential influence of confounding factors, such as motion artifacts, illumination fluctuations (under- and overexposure), and loss of region of interest prior to heart rate evaluation. This reduced the amount of data we evaluated for heart rate to 56.1% of its original volume. In artifact-free time segments, the mean difference between the pulse oximetry and the imaging photoplethysmography-based system for 1 s sampling intervals resulted in -0.2 bpm (95% CI -0.8 to 0.4, LOA ± 12.2). For the clinical standard of 8 s averaging time, the mean difference resulted in -0.09 bpm (95% CI -0.7 to 0.6, LOA ± 10.1). These results match the medical standards. While further research is needed to increase the range of measurable vital parameters and more diverse patient collectives need to be considered in the future, we could demonstrate very high accuracy for non-contact heart rate measurement in newborn infants in the clinical setting, provided artifacts are excluded. In particular, performing a priori signal assessment helps make clinical measurements safer by identifying unreliable readings.