Objective This study was performed to determine whether the efficacy and safety of medical management of uncomplicated peritonsillar abscess (PTA) presenting in the emergency department is equivalent to medical plus surgical therapy. Study Design Case series with chart review. Setting Southern California Permanente Medical Group (SCPMG). Subjects and Methods Upon successful completion of a prospective study comparing medical treatment (MT) to surgical treatment (ST) of PTA in 2008, MT was adopted by 12 SCPMG centers while 7 centers continued standard surgical drainage. Clinical outcomes are now reviewed on a random sampling of 211 patients with PTA treated with MT and 96 patients treated with ST between 2008 and 2013 at the respective medical centers. Patients were treated with intravenous (IV) fluids, weight-appropriate IV ceftriaxone, clindamycin, and dexamethasone, and then discharged on clindamycin × 10 days (MT). Patients in the ST group received MT but also surgical drainage. Primary end points were complication rates and failure rates. Results MT and ST resulted in no significant difference in treatment success or complications. However, patients in the MT group obtained significantly less liquid opioid prescriptions (MT, 30.8 ± 5.65; ST, 77.75 ± 13.41; P < .0001), reported fewer sore days (MT, 4.48 ± 0.27; ST, 5.77 ± 0.49; P = .0004), and required less days off from work (MT, 3.4 ± 0.44; ST, 4.9 ± 0.82; P = .044). Conclusions Compared to ST, MT appears to be equally safe and efficacious, with less pain, opioid use, and days off work, especially if patients with PTA present without trismus. MT for PTAs reduces the possibility of surgical complications, as well as the cost and inconvenience associated with ST.