Aliasing effects due to time-discrete capturing of amplitude-modulated light with a digital image sensor are perceived as flicker by humans. Especially when observing these artifacts in digital mirror replacement systems, they are annoying and can pose a risk. Therefore, ISO 16505 requires flicker-free reproduction for 90% of people in these systems. Various psychophysical studies investigate the influence of large-area flickering of displays, environmental light, or flickering in television applications on perception and concentration. However, no detailed knowledge of subjective annoyance/irritation due to flicker from camera-monitor systems as a mirror replacement in vehicles exist so far, but the number of these systems is constantly increasing. This psychophysical study used a novel data set from real-world driving scenes and synthetic simulation with synthetic flicker. More than 25 test persons were asked to quantify the subjective annoyance level of different flicker frequencies, amplitudes, mean values, sizes, and positions. The results show that for digital mirror replacement systems, human subjective annoyance due to flicker is greatest in the 15 Hz range with increasing amplitude and magnitude. Additionally, the sensitivity to flicker artifacts increases with the duration of observation.