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To determine the degree to which focally elevated tibiofemoral joint contact stress is reduced by using a frontal plane realigning brace. Fifteen volunteers (9 women) with unicompartmental tibiofemoral osteoarthritis underwent weight‐bearing radiographic imaging at 15–20° and 5–10° of knee flexion with and without an UnloaderOne knee brace. Discrete element analysis was used to estimate compartment‐specific contact stress distributions. Paired t‐tests were used to assess the differences in mean contact stress and contact stress distributions, comparing the braced and unbraced conditions. The mean ± SD age was 56.1 ± 6.4 years and body mass index was 28.4 ± 4.5 kg/m2. Twelve of 15 participants were fit with braces set to unload the medial compartment. For the 15–20° condition, the mean contact stress in the compartment of interest did not significantly change (0.08 ± 0.35 MPa; P= 0.410). Also at 5–10° flexion, the mean contact stress in the compartment of interest did not significantly change with use of the brace (0.24 ± 0.45 MPa; P= 0.175). This is the first study of the effects of a frontal plane realignment brace on in vivo articular contact stress in native human knees. Using the off‐the‐shelf brace tested, there were no changes in compartmental tibiofemoral contact stress distributions at either 15–20° or 5–10° of knee flexion, revealing no redistribution of contact stress away from the compartment of interest. These findings indicate that the brace that was studied was ineffective for redistributing tibiofemoral contact stress. Further research is necessary to determine whether double‐upright or customized frontal plane braces are effective in redistributing compartmental articular contact stress.