Background: Current literature provides little consensus on universal guidelines for first-line treatment of chronic subdural hematomas (cSDH). However, administration of local tissue plasminogen activator (tPA) may enhance the traditional method of twist drill drainage (TDD). The study aims to explore the efficacy of TDD with and without tPA, at achieving clinically relevant drainage (200mL) and reducing recurrence of cSDH. Methods: A retrospective review of patients (N=34) with cSDH is presented. Patients who received TDD with tPA (n=17) were identified and matched, based primarily on age and hematoma volume, to a control group (n=17), TDD without tPA. Variables of interest include initial hematoma volume, volume drained, length of stay, and recurrence rates. Descriptive analysis was run. Results: Average age for patients was 74.6 with 76% male. Mean drainage volumes for the tPA cohort was 381.6mL and TDD without tPA cohort was 151.3mL. The addition of tPA resulted in drainage volumes nearly double (1.9x) the clinically relevant amount and had low recurrence rates (12.5%). TDD without tPA failed to result in clinically relevant drainage and had a recurrence rate of 52.9%. Average length of stay differed by two days (9.71 tPA; 7.71 control). Conclusions: TDD with tPA was effective at treating cSDH in our population.