Importance: Some marketing materials for yellow-lens night-driving glasses claim that they increase nighttime road visibility and reduce oncoming headlight glare (HLG). However, there is no scientific evidence to support these claims. Objective: To measure the association between yellow-lens glasses and the detection of pedestrians with and without an oncoming HLG, using a driving simulator equipped with a custom HLG simulator. Design, Setting, and Participants: A single-center cohort study was conducted between September 8, 2016, and October 25, 2017, at the Schepens Eye Research Institute. A total of 22 individuals participated in the study, divided into groups to determine response to a pedestrian wearing a navy blue shirt by younger individuals and, to control for participant's age and the interaction of the shirt color with the filter, response to a pedestrian wearing an orange shirt by a group of younger and older participants. Exposures: Participants drove scripted night-driving scenarios, 3 times with 3 commercially available yellow-lens glasses and once with clear-lens glasses, with the HLG simulator turned on and off. A total of 8 conditions were used for each participant. Main Outcomes and Measures: Pedestrian detection response time. Results: The 22 participants who completed the study included 12 younger (mean [SD] age, 28  years; 6 men) individuals who responded to a pedestrian wearing a dark navy blue shirt, as well as 6 younger (mean [SD] age, 27  years; 4 men) and 4 older (mean [SD], 70  years; all men) participants who responded to a pedestrian in an orange shirt. All participants had normal visual acuity (mean [SD], -0.05 [0.06] logMAR). No significant difference in response time with yellow lens was found in all experiment conditions; younger participants for dark navy blue shirt pedestrians (F1,33 = 0.59; P = .45), orange shirt pedestrians (F1,15 = 0.13; P = .72), and older participants for orange shirt pedestrians (F1,9 = 0.84; P = .38). Among all participants (n = 22), no significant main effect of yellow lenses was found (F1,63 = 0.64; P = .42). In all measuring conditions, the response times with the yellow lenses were not better than with the clear lenses. Significant main effects of HLG were found with dark navy blue shirt pedestrian condition for young participants (F1,33 = 7.34; P < .001) and with orange shirt pedestrian condition for older individuals (F1,9 = 75.32; P < .001), where the difference in response time between with and without HLG was larger for older (1.5 seconds) than younger (0.3 seconds) participants. Conclusions and Relevance: Using a driver simulator equipped with an HLG simulator, yellow-lens night-driving glasses did not appear to improve pedestrian detection at night or reduce the negative effects of HLG on pedestrian detection performance. These findings do not appear to support having eye care professionals advise patients to use yellow-lens night-driving glasses.