Background Cystic adventitial disease (CAD) is a rare condition that affects arteries and veins. The etiology remains controversial and several treatment methods have been described. By understanding the pathogenesis of CAD, we can improve the surgical treatment, reduce recurrence rates, and improve patient outcomes. The objective of this study was to perform a systematic review of the world's literature. Methods We searched across multiple scientific databases and cross-referenced each article to collect the world's literature on CAD. Studies included were those that reported a case or case series of CAD. Each article was analyzed for site of CAD, patient demographic data, type of imaging, surgical management, presence of a joint connection on imaging or at surgery, and recurrences. A regression analysis was used to identify risk factors for cyst recurrence. Results We identified 503 reports (724 patients), which were included in our analysis. The most common vessel affected was the popliteal artery with 587 cysts. The mean age was 46 (range, 5-80) years with a male-to-female ratio of approximately 4:1. Magnetic resonance imaging (MRI) or angiography was performed for 182 cysts and conventional angiography was the most advanced imaging modality used in 355 patients who did not receive a MRI or computed tomography scan as part of their assessment. Multiple types of surgical interventions were reported with the most common being cyst resection and saphenous vein graft reconstruction (204 cases). There were 122 joint connections (17%) identified. Sixty-five patients (9%) developed at least one cyst recurrence or persistence. Percutaneous surgery (aspiration or angioplasty) was found to be a risk factor for cyst recurrence (odds ratio, 13.7; 95% confidence interval, 6.5-29.0; P < .0001). Because of the rarity of this condition, publications were limited to level IV evidence consisting of case series and case reports. Several reports had short or no follow-up and few patients had postoperative MRI. These limitations likely underestimate the true rate of cyst recurrence or persistence. Conclusions This article provides a comprehensive review of the world's literature on CAD, which can serve as a baseline for future studies. When analyzed in the context of the literature, this systematic review supplies further evidence that CAD adheres to the articular (synovial) theory. We believe that knowledge of these joint connections can simplify treatment, reduce recurrence rates, and improve patient outcomes.