Study Design Randomized clinical trial. Objectives To determine whether manipulation of the proximal or distal tibiofibular joint would change ankle dorsiflexion range of motion and functional outcomes over a 3-week period in individuals with chronic ankle instability. Background Altered joint arthrokinematics may play a role in chronic ankle instability dysfunction. Joint mobilization or manipulation may offer the ability to restore normal joint arthrokinematics and improve function. Methods Forty-three participants (mean ± SD age, 25.6 ± 7.6 years; height, 174.3 ± 10.2 cm; mass, 74.6 ± 16.7 kg) with chronic ankle instability were randomized to proximal tibiofibular joint manipulation, distal tibiofibular joint manipulation, or a control group. Outcome measures included ankle dorsiflexion range of motion, the single-limb stance on foam component of the Balance Error Scoring System, the step-down test, and the Foot and Ankle Ability Measure sports subscale. Measurements were obtained prior to the intervention (before day 1) and following the intervention (on days 1, 7, 14, and 21). Results There was no significant change in dorsiflexion between groups across time. When groups were pooled, there was a significant increase (P<.001) in dorsiflexion at each postintervention time interval. No differences were found among the Balance Error Scoring System foam, step-down test, and Foot and Ankle Ability Measure sports subscale scores. Conclusions The use of a proximal or distal tibiofibular joint manipulation in isolation did not enhance outcome effects beyond those of the control group. Collectively, all groups demonstrated increases in ankle dorsiflexion range of motion over the 3-week intervention period. These increases might have been due to practice effects associated with repeated testing. Level of Evidence Therapy, level 2b-. J Orthop Sports Phys Ther 2012;42(2):125–134. doi:10.2519/jospt.2012.3729