Introduction: Most running-related injuries are believed to be caused by abrupt changes in training load, compounded by biomechanical movement patterns. Wearable technology has made it possible for runners to quantify biomechanical loads (e.g., peak positive acceleration; PPA) using commercially available inertial measurement units (IMUs). However, few devices have established criterion validity. The aim of this study was to assess the validity of two commercially available IMUs during running. Secondary aims were to determine the effect of footwear, running speed, and IMU location on PPA.Materials and Methods: Healthy runners underwent a biomechanical running analysis on an instrumented treadmill. Participants ran at their preferred speed in three footwear conditions (neutral, minimalist, and maximalist), and at three speeds (preferred, +10%, −10%) in the neutral running shoes. Four IMUs were affixed at the distal tibia (IMeasureU-Tibia), shoelaces (RunScribe and IMeasureU-Shoe), and insole (Plantiga) of the right shoe. Pearson correlations were calculated for average vertical loading rate (AVLR) and PPA at each IMU location.Results: The AVLR had a high positive association with PPA (IMeasureU-Tibia) in the neutral and maximalist (r = 0.70–0.72; p ≤ 0.001) shoes and in all running speed conditions (r = 0.71–0.83; p ≤ 0.001), but low positive association in the minimalist (r = 0.47; p < 0.05) footwear condition. Conversely, the relationship between AVLR and PPA (Plantiga) was high in the minimalist (r = 0.75; p ≤ 0.001) condition and moderate in the neutral (r = 0.50; p < 0.05) and maximalist (r = 0.57; p < 0.01) footwear. The RunScribe metrics demonstrated low to moderate positive associations (r = 0.40–0.62; p < 0.05) with AVLR across most footwear and speed conditions.Discussion: Our findings indicate that the commercially available Plantiga IMU is comparable to a tibia-mounted IMU when acting as a surrogate for AVLR. However, these results vary between different levels of footwear and running speeds. The shoe-mounted RunScribe IMU exhibited slightly lower positive associations with AVLR. In general, the relationship with AVLR improved for the RunScribe sensor at slower speeds and improved for the Plantiga and tibia-mounted IMeasureU sensors at faster speeds.