Background Maintaining adequate situation awareness is crucial for patient safety. Previous studies found that the use of avatar-based monitoring (Visual Patient Technology) improved the perception of vital signs compared to conventional monitoring showing numerical and waveform data; and was further associated with a reduction of perceived workload. In this study, we aimed to evaluate the effectiveness of Visual Patient Technology on perceptive performance and perceived workload when monitoring multiple patients at the same time, such as in central station monitors in intensive care units or operating rooms. Methods A prospective, within-subject, computer-based laboratory study was performed in two tertiary care hospitals in Switzerland in 2018. Thirty-eight physician and nurse anesthetists volunteered for the study. The participants were shown four different central monitor scenarios in sequence, where each scenario displayed two critical and four healthy patients simultaneously for 10 or 30 seconds. After each scenario, participants had to recall the vital signs of the critical patients. Perceived workload was assessed with the National Aeronautics and Space Administration Task-Load-Index (NASA TLX) questionnaire. Results In the 10-second scenarios, the median number of remembered vital signs significantly improved from 7 to 11 using avatar-based versus conventional monitoring with a mean of differences of 4 vital signs, 95% confidence interval (CI) 2 to 6, p < 0.001. At the same time, the median NASA TLX scores were significantly lower for avatar-based monitoring (67 vs. 77) with a mean of differences of 6 points, 95% CI 0.5 to 11, p = 0.034. In the 30-second scenarios, vital sign perception and workload did not differ significantly. Conclusions In central monitor multiple patient monitoring, we found a significant improvement of vital sign perception and reduction of perceived workload using Visual Patient Technology, compared to conventional monitoring. The technology enabled improved assessment of patient status and may, thereby, help to increase situation awareness and enhance patient safety.