Prolonged non-contact camera-based monitoring in critically ill patients presents unique challenges, but may facilitate safe recovery. A study was designed to evaluate the feasibility of introducing a non-contact video camera monitoring system into an acute clinical setting. We assessed the accuracy and robustness of the video camera-derived estimates of the vital signs against the electronically-recorded reference values in both day and night environments. We demonstrated non-contact monitoring of heart rate and respiratory rate for extended periods of time in 15 post-operative patients. Across day and night, heart rate was estimated for up to 53.2% (103.0 h) of the total valid camera data with a mean absolute error (MAE) of 2.5 beats/min in comparison to two reference sensors. We obtained respiratory rate estimates for 63.1% (119.8 h) of the total valid camera data with a MAE of 2.4 breaths/min against the reference value computed from the chest impedance pneumogram. Non-contact estimates detected relevant changes in the vital-sign values between routine clinical observations. Pivotal respiratory events in a post-operative patient could be identified from the analysis of video-derived respiratory information. Continuous vital-sign monitoring supported by non-contact video camera estimates could be used to track early signs of physiological deterioration during post-operative care.