SIGNIFICANCE Prior studies have demonstrated the effectiveness of vergence-accommodative therapy in the treatment of convergence insufficiency (CI). These results show the changes in brain activation following therapy through the use of functional magnetic resonance imaging (fMRI). PURPOSE The purpose of this study was to investigate changes in brain activation following office-based vergence-accommodative therapy versus placebo therapy for CI using the blood oxygenation level-dependent signal from fMRI. METHODS Adults (n = 7, aged 18 to 30 years) with symptomatic CI were randomized to 12 weeks of vergence-accommodative therapy (n = 4) or placebo therapy (n = 3). Vergence eye movements were performed during baseline and outcome fMRI scans. RESULTS Before therapy, activation (z score ≥ 2.3) was observed in the occipital lobe and areas of the brain devoted to attention, with the largest areas of activation found in the occipital lobe. After vergence-accommodative therapy, activation in the occipital lobe decreased in spatial extent but increased in the level of activation in the posterior, inferior portion of the occipital lobe. A new area of activation appeared in the regions of the lingual gyrus, which was not seen after placebo therapy. A significant decrease in activation was also observed in areas of the brain devoted to attention after vergence-accommodative therapy and to a lesser extent after placebo therapy. CONCLUSIONS Observed activation pre-therapy consistent with top-down processing suggests that convergence requires conscious effort in symptomatic CI. Decreased activation in these areas after vergence-accommodative therapy was associated with improvements in clinical signs such as fusional vergence after vergence-accommodative therapy. The increase in blood oxygen level-dependent response in the occipital areas following vergence-accommodative therapy suggests that disparity processing for both depth and vergence may be enhanced following vergence-accommodative therapy.