OBJECTIVE: Evaluate prescribing practices and risk factors for treatment failure in obese patients treated for purulent cellulitis with oral antibiotics in the outpatient setting. DESIGN: Retrospective, multicenter, observational cohort. SETTING: Emergency departments, primary care, and urgent care sites throughout Michigan. PATIENTS: Adult patients with a body mass index of ≥ 30 kg/m who received ≥ 5 days of oral antibiotics for purulent cellulitis were included. Key exclusion criteria were chronic infections, antibiotic treatment within the past 30 days, and suspected polymicrobial infections. METHODS: Obese patients receiving oral antibiotics for purulent cellulitis between February 1, 2020, and August 31, 2023, were assessed. The primary objective was to describe outpatient prescribing trends. Secondary objectives included comparing patient risk factors for treatment failure and safety outcomes between patients experiencing treatment success and those experiencing treatment failure. RESULTS: Two hundred patients were included (Treatment success, n = 100; Treatment failure, n = 100). Patients received 11 antibiotic regimens with 26 dosing variations; 45.5% were inappropriately dosed. Sixty-seven percent of patients received MRSA-active therapy. Treatment failure was similar between those appropriately dosed (46.4%) versus under-dosed (54.4%) ( = 0.256), those receiving 5-7 days of therapy (47.1%) versus 10-14 days (54.4%) ( = 0.311), and those receiving MRSA-active therapy (52.2%) versus no MRSA therapy (45.5%) ( = 0.367). Patients treated with clindamycin were more likely to experience treatment failure (73.7% vs 47.5%, = 0.030). CONCLUSIONS: Nearly half of antimicrobial regimens prescribed for outpatient treatment of cellulitis in patients with obesity were suboptimally prescribed. Opportunities exist to optimize agent selection, dosing, and duration of therapy in this population.