Aberrant synaptic plasticity in corticostriatal circuits may be an underlying mechanism of anxiety disorders such as obsessive-compulsive disorder (OCD). We explored the effect of anterior capsulotomy in an OCD patient on long-term depression (LTD) in the striatum. Dual microelectrodes were used to record and stimulate in the region of the anterior limb of the internal capsule and ventral striatum. Single pulses were used to evoke field excitatory postsynaptic potentials (fEPSPs) and high-frequency stimulation (HFS) was used to induce LTD before and after the surgical procedure on the initial side. Whereas striatal fEPSPs underwent LTD in response to HFS before capsulotomy, there was an attenuation of LTD in response to the same stimulus after the procedure concomitant with the patient’s report of a reduction in anxiety. Our observation of human striatal LTD attenuation concomitant with reduced anxiety following anterior capsulotomy suggests that reduction in synaptic plasticity is related to an acute improvement of OCD symptoms.