Management of nonemergent, nonacute subdural hematomas (SDHs) ranges from observation to burr-hole evacuation or craniotomy, but recurrence rates are high. We evaluated the safety and efficacy of tranexamic acid (TXA) for the treatment of residual SDHs after bedside twist-drill evacuation. We performed a retrospective analysis of a prospectively maintained database from November 2013 to November 2014 for all patients who underwent placement of a bedside subdural evacuating port system (SEPS) followed by treatment with oral TXA (650 mg daily). All demographics, evidence of venous thromboembolism, and volumes of pertinent computed tomography were obtained. Twenty subdural hematomas in 14 patients met the inclusion criteria for this study. Most SDHs were mixed density. Mean SDH volume on presentation was 145.96 ± 40.22 cm(3) with a mean midline shift of 9.44 ± 4.84 mm. Mean volumes decreased to 80.00 ± 31.96 cm(3) and midline shift improved to 4.44 ± 3.29 mm after SEPS placement (P < 0.0001 and P= 0.0046). All patients were placed on TXA after their procedure. Mean follow-up with computed tomography was 92.1 ± 27.5 days, and mean SDH volume at last follow-up was 7.41 ± 15.54 cm(3) with a mean midline shift of 0.19 ± 0.69 mm (P < 0.0001 and P= 0.0002). Percent volume reduction was significantly higher after TXA than after SEPS (91.31% vs. 40.74%; P < 0.0001). No increase or delayed recurrence of the SDH was noted during TXA treatment. All but 1 clinical presenting symptom improved at follow-up. No venous thromboembolisms were noted among the patients. In our pilot study, chronic SDH volumes were reduced by 40.74% after SEPS drainage. The residual volume was reduced by an additional 91.31% during oral TXA treatment. No patients developed delayed recurrence or expansion of their SDHs. Further prospective studies are needed to evaluate the role of TXA for adjunctive treatment of chronic SDHs.