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 < .01, all ${\eta }_{\text{part}}^2>.3$). No main effect for FSP or any significant interaction effect indicating FSP-specific differences between FFS or RFS was found (all P > .05, all ${\eta }_{\text{part}}^2<.07$), except for LDH (P < .001, ${\eta }_{\text{part}}^2=.77$). Conclusions: NSE, S100B, and LDH concentration increased in the short term after running and returned to normal in 24 h. FSP with varying impact forces does not influence the increase of these biomarkers. LDH findings favor peripheral origins, but mixed effects are possible. Thus, further research is needed to estimate the risk of mild traumatic encephalopathy.