This is the first controlled quantitative analysis on the visual distraction effects of audio-visual route guidance in simulated, but ecologically realistic driving scenarios with dynamic maneuvers and self-controlled speed (N = 24). The audio-visual route guidance system under testing passed the set verification criteria, which was based on drivers’ preferred occlusion distances on the test routes. There were no significant effects of an upcoming maneuver instruction location (up, down) on the in-car display on any metric or on the experienced workload. The drivers’ median occlusion distances correlated significantly with median incar glance distances. There was no correlation between drivers’ median occlusion distance and intolerance of uncertainty but significant inverse correlations between occlusion distances and age as well as driving experience were found. The findings suggest that the visual distraction effects of audio-visual route guidance are low and provide general support for the proposed testing method.