Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that has a substantial impact on patients’ quality of life. As the exact pathogenesis remains unclear, treatment is complex and not yet standardized. Objectives: The aim of this study was to describe patient characteristics and to broadly examine trends in treatment response of various therapeutic strategies in patients with HS in a single academic referral center in the southern USA. Methods: A retrospective chart review was conducted of a cohort of HS patients seen in a faculty general dermatology practice with academic affiliation to Baylor University Medical Center in Dallas, TX, between February 2015 and February 2018. Patient demographics, clinical features, prescribed treatments, and response to treatment were analyzed using the Pearson χ2 test or Fisher exact test, and by the Mann-Whitney U test for categorical and continuous variables, respectively. Results: A total of 149 patients (113 females, 36 males) were included. Hurley stages I, II, and III were diagnosed in 29.6, 36.5, and 33.9% of patients, respectively. 44.2% of patients had a positive family history of HS, 39.5% of patients were current or former smokers, and 52.8% reported alcohol use. 80.9% of patients were overweight or obese (BMI ≥25), compared to 68.5% in Texas in 2016 (p = 0.0012). The most frequently prescribed treatments were oral antibiotic therapy (83.9%), topical antibiotic therapy (74.5%), metabolic medications such as metformin/zinc (67.1%), intralesional Kenalog (63.1%), and biologic therapies (tumor necrosis factor-α inhibitors; TNF-α inhibitors; 49%). In examining the response rate, patients with disease localized to the buttocks had significantly higher response rates (60.4 vs. 25%, p = 0.043) and approached statistical significance in responders versus nonresponders in treatment with biologics (p = 0.0632) when compared against all other treatments. Conclusions: HS is a complex inflammatory skin condition associated with obesity and smoking. In this cohort, the most frequently prescribed therapies were oral and topical antibiotics. However, the use of biologic agents (TNF-α inhibitors) appears to be associated with the most significant treatment response. Key Points: This is the first study to evaluate trends in treatment response of various therapeutic strategies in HS patients at an academic referral center in Dallas, TX, a unique geographic region of the southern USA. Biologic therapy (TNF-α inhibitor) appears to be associated with the most significant treatment response.