This study examined the effect of the stimulus-response (S-R) compatibility of pedestrian collision warnings presented via different sensory modalities in a driving simulator. Despite the well-established fact that reaction times (RT) are faster under S-R compatible conditions, the majority of collision warning research has used S-R incompatible warnings (i.e., the warning comes from the direction of the obstacle to be avoided not the desired response direction). Thirty-two participants in a fixed-base driving simulator drove on a three-lane urban road in which pedestrians randomly walked from the sidewalk into the roadway. Collision warnings in two different modalities (tactile and auditory) were compared with a no warning condition. Participants were equally divided into one of four conditions representing all combinations of two levels of warning S-R compatibility (compatible and incompatible) and two levels of warning timing (early and late). For early warnings, incompatible warnings were most effective as shown by a significantly shorter steering RT and larger clearance distance. For late warnings, compatible warnings were most effective. For early warnings, RTs were significantly faster in the tactile condition. The relationship between collision warning effectiveness and S-R compatibility in driving is dependent on whether the driver has time to evaluate the situation before collision will occur. Our findings have important implications for the design of effective tactile and auditory collision warning systems. However, further research is needed to determine if these effects occur in more representative driving conditions (e.g., lower pedestrian incursion rate and unreliable warnings).