Purpose: Foot-strike patterns (FSP) in running are related to certain impact kinetics during ground contact. A rear-foot strike (RFS) has been associated with higher impact forces, whereas a forefoot strike (FFS) is assumed to minimize these impact forces. This study investigated the effects of running with RFS or FFS on impact-sensitive neuronal biomarkers S100 calcium-binding protein B (S100B), neuron-specific enolase (NSE), and lactate dehydrogenase (LDH). Methods: In this randomized crossover study, 18 healthy recreational runners (14 male, mean [SD] age 28.2 [4.7] y, body mass index 22.8 [1.9]) ran 2 separate 5-mile runs with RFS or FFS, respectively. Blood samples were taken before (pre), 30 min after (post 0), and 24 h after (post 24) the run. S100B, NSE, and LDH concentrations were determined and analyzed (3 × 2 data model). Results: S100B, NSE, and LDH concentrations increased from pre to post 0 and decreased within 24 h back to the baseline level, demonstrating a significant time effect (all P .3). No main effect for FSP or any significant interaction effect indicating FSP-specific differences between FFS or RFS was found (all P >.05, all η2part