Background: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by thunderclap headaches associated with radiographic evidence of reversible segmental vasoconstriction of cerebral arteries. RCVS is associated with both ischemic and hemorrhagic strokes. Methods: We present a case of probable RCVS with intracerebral hemorrhage (ICH) in the setting of antidepressant medication use that was successfully managed with minimally invasive surgery plus intra-hematomal delivery of recombinant tissue plasminogen activator (rtPA). Results: A 45-year-old woman underwent an elective repair of a left superior semicircular canal dehiscence. On postoperative day 3 she developed a severe headache followed by acute onset of left face and body hemiparesis. Head computed tomography (CT) showed a large acute ICH in the right basal ganglia. Due to concern for impending cerebral herniation, the patient underwent stereotactic aspiration of ICH and placement of an indwelling catheter for intra-hematomal delivery of rtPA. Seven doses of 1 mg rtPA were administered via the intraparechymal catheter with significant clot reduction. Repeat cerebral angiogram showed arterial beading in both the anterior and posterior circulation. Conclusion: RCVS is an important diagnosis to consider in cases of ICH without identifiable cause even when initial angiography is normal. In severe cases, secondary management of ICH plays an important role, including minimally invasive surgical intervention to reduce clot volume and minimize perihematomal edema.