OBJECTIVES: The purpose of this study was to develop a patient-reported outcome (PRO) instrument to assess Acute Bacterial Skin and Skin Structure Infection (ABSSSI) symptoms in patients in clinical trials of antibacterial drugs, consistent with FDA PRO Guidance. METHODS: A comprehensive review of the literature and interviews with nine US and European clinical experts informed the development of a concept elicitation (CE) interview guide, and a hypothetical conceptual framework and disease model exploring patients' experience with symptoms of ABSSSI. CE was based on telephone interviews with 34 patients, after which saturation of emergent concepts was reached.  Items and response options were generated based on the qualitative data and a draft instrument was prepared with input and review from an international project team of academic and industry antibacterial experts. Subsequently, cognitive debriefing interviews were conducted with 15 ABSSSI patients and 3 clinical experts to assess item readability, relevance, comprehensiveness, and content validity. Items were edited based on feedback from the patients. RESULTS: CE subtypes were evaluated and consisted of 13 (38.2%) patients with major abscess, 12 (35.3%) with wound infection, and 9 (26.5%) with cellulitis.  In terms of severity, the majority (79.4%) of infections were rated as moderate by clinicians. The mean age of patients was 38.8 years; 64.7% male. Symptoms were common across all ABSSSI subtypes and supported the saturation of concepts. Items were generated for the PRO Instrument using patient terminology. Subsequent cognitive debriefing with patients demonstrated that the items were understandable, relevant, and interpreted as intended. CONCLUSIONS: SKINFECT is a PRO instrument developed to evaluate ABSSSI patient symptoms and functioning in clinical studies with documented evidence of content validity. Qualitative data from patients and input from experts formed the basis of the SKINFECT’s structure and item pool, and it is now ready for psychometric reliability and validity testing.