Mixed-use urban environments, such as arterial roads with adjacent commercial land uses, represent crash locations with the highest risk. These locations are often characterized by high volumes of motor vehicle traffic, on-street parking, and interactions with multiple road user groups such as pedestrians, cyclists, and public transportation. The objective of this study was to investigate previously identified crash risk factors for mixed-use urban environments and assess how parking occupancy, center medians, and cyclist volume influence performance and workload in a driving simulator study. Thirty participants were recruited for the study. Participants completed 6 drives that presented different combinations of cyclist volume, median condition, and parking occupancy. Incorporated into the simulator drives was a secondary peripheral detection task (PDT) designed to measure mental workload. Participants provided subjective assessments of workload using the Rating Scale Mental Effort (RSME). Mean lateral lane position was found to significantly vary across the 3 independent variables of parking occupancy, cyclist volume, and median conditions. No significant changes were identified for mean speed across the conditions. Subjective and objective measures of workload identified changes due to the presence of cyclists with slower reaction times for the PDT task when cyclists were present. The findings provide insight into the interaction of road design elements in mixed-use urban road environments and demonstrate that increasingly complex environments increase driver demand. This has important road design implications for mixed-use arterial roads, which are often characterized by complex interactions between multiple road user groups.