To examine the effects of increased strength on mechanical work, the metabolic cost of transport (Cost), and mechanical efficiency (ME) during running. Fourteen physically active men (22.0 ± 2.0 years, 79.3 ± 11.1 kg) were randomized to a strength-training group (SG, n = 7), who participated in a maximal strength training protocol lasting 8 weeks, and a control group (CG, n = 7), which did not perform any training intervention. Metabolic and kinematic data were collected simultaneously while running at a constant speed (2.78 m·s-1). The ME was defined as the ratio between mechanical power (Pmec) and metabolic power (Pmet). The repeated measures two-way ANOVA did not show any significant interaction between groups, despite some large effect sizes (d): internal work (Wint, p = 0.265, d = -1.37), external work (Wext, p = 0.888, d = 0.21), total work (Wtot, p = 0.931, d = -0.17), Pmec (p = 0.917, d = -0.17), step length (SL, p = 0.941, d = 0.24), step frequency (SF, p = 0.814, d = -0.18), contact time (CT, p = 0.120, d = -0.79), aerial time (AT, p = 0.266, d = 1.12), Pmet (p = 0.088, d = 0.85), and ME (p = 0.329, d = 0.54). The exception was a significant decrease in Cost (p = 0.047, d = 0.84) in SG. The paired t-test and Wilcoxon test only detected intragroup differences (pre- vs. post-training) for SG, showing a higher CT (p = 0.041), and a lower Cost (p = 0.003) and Pmet (p = 0.004). The results indicate that improved neuromuscular factors related to strength training may be responsible for the higher metabolic economy of running after 8 weeks of intervention. However, this process was unable to alter running mechanics in order to indicate a significant improvement in ME.