OBJECTIVE: To compare the efficacy and safety of multiple treatment modalities for the management of chronic subdural hematoma (CSDH) patients. BACKGROUND: Current management strategies of CSDHs remain widely controversial. Treatment options vary from medical therapy and bedside procedures to major operative techniques. METHODS: We searched MEDLINE (PubMed and Ovid), EMBASE, CINAHL, Google scholar, and the Cochrane library from January 1970 through February 2013 for randomized and observational studies reporting one or more outcome following the management of symptomatic patients with CSDH. Independent reviewers evaluated the quality of studies and abstracted the data on the safety and efficacy of percutaneous bedside twist-drill drainage, single or multiple operating room burr holes, craniotomy, corticosteroids as a main or adjuvant therapy, use of drains, irrigation of the hematoma cavity, bed rest, and treatment of recurrences following CSDH management. Mortality, morbidity, cure, and recurrence rates were examined for each management option. Randomized, prospective, retrospective, and overall observational studies were analyzed separately. Pooled estimates, confidence intervals (CIs), and relative risks (RRs) were calculated for all outcomes using a random-effects model. RESULTS: A total of 34,829 patients from 250 studies met our eligibility criteria. Sixteen trials were randomized, and the remaining 234 were observational. We included our unpublished single center series of 834 patients. When comparing percutaneous bedside drainage to operating room burr hole evacuation, there was no significant difference in mortality (RR, 0.69; 95% CI, 0.46-1.05; P = 0.09), morbidity (RR, 0.45; 95% CI, 0.2-1.01; P = 0.05), cure (RR, 1.05; 95% CI, 0.98-1.11; P = 0.15), and recurrence rates (RR, 1; 95% CI, 0.66-1.52; P = 0.99). Higher morbidity was associated with the adjuvant use of corticosteroids (RR, 1.97; 95% CI, 1.54-2.45; P = 0.005), with no significant improvement in recurrence and cure rates. The use of drains following CSDH drainage resulted in a significant decrease in recurrences (RR, 0.46; 95% CI, 0.27-0.76; P = 0.002). Craniotomy was associated with higher complication rates if considered initially (RR, 1.39; 95% CI, 1.04-1.74; P = 0.01); however, craniotomy was superior to minimally invasive procedures in the management of recurrences (RR, 0.22; 95% CI, 0.05-0.85; P = 0.003). CONCLUSIONS: Percutaneous bedside twist-drill drainage is a relatively safe and effective first-line management option. These findings may result in potential health cost savings and eliminate perioperative risks related to general anesthetic.