Background: In cases of oral antibiotic-resistant infection of the hand, we propose utilizing a heated, moist maceration dressing to help shorten and simplify the in-hospital clinical course by increasing the efficacy of antibiotic deliverance to infection sites, increasing the success of nonoperative management, and decreasing eradication time of infection of the hand. Methods: Fifty-six patients older than 18 years of age who presented with hand infections requiring inpatient intravenous antibiotics at our suburban academic hospital over a 30-month period were included and randomly assigned to either the maceration dressing group or the standard treatment group. Maceration dressings included warm and moist gauze, kerlix, webril, Orthoglass, Aqua K Pad, and sling. Results: Fifty-two patients who were mostly male and younger than 60 years of age were included. Patients who used the maceration dressing had significantly shorter hospital lengths of stay ( P = .02) and intravenous antibiotics duration before transition to oral antibiotics ( P = .04), and decreased need for formal operating room irrigation and debridement to obtain source control ( P = .02) compared to patients treated with the standard dressing. Post-hoc analysis yielded improved outcomes when using the maceration dressing regardless of whether initial bedside incision and drainage was needed to decompress a superficial abscess or not. Conclusion: The maceration dressing can be used along with proper intravenous antibiotic treatment to improve the treatment course of patients with hand infections regardless of whether the patient needs an initial bedside incision and drainage or not. Level of Evidence: Therapeutic Level II.