Cerebrospinal fluid-venous fistula (CVF) is a recently described cause of spontaneous intracranial hypotension (SIH). Surgical ligation of CVF has been reported, but clinical outcomes are not well described. To determine the clinical efficacy of surgical ligation for treatment of CVF. Outcomes metrics were collected in this prospective, single-arm, cross-sectional investigation. Inclusion criteria were as follows: diagnosis of SIH, demonstration of CVF on myelography, and surgical treatment of CVF. Pre- and postoperative headache severity was assessed with the Headache Impact Test (HIT-6), a validated headache scale ranging from 36 (asymptomatic) to 78 (most severe). Patient satisfaction with treatment was measured with Patient Global Impression of Change (PGIC). Twenty subjects were enrolled, with mean postoperative follow-up at 16.0±9.7 mo. All CVFs were located in the thoracic region (between T4 and T12). Pretreatment headache severity was high (mean HIT-6 scores 65±6). Surgical treatment resulted in marked improvement in headache severity (mean HIT-6 change of -21±-9, mean postoperative HIT-6 of 44±8). Of subjects with baseline headache scores in the most severe category, 83% showed a major improvement in severity (transition to the lowest 2 severity categories) after surgery. All subjects (100%) reported clinically significant levels of satisfaction with treatment (PGIC score 6 or 7); 90% reported the highest level of satisfaction. There were no short- or long-term complications or 30-d readmissions. Surgical ligation is highly effective for the treatment of SIH due to CVF. Larger controlled trials with longer follow-up period are indicated to better assess its long-term efficacy and safety profile.