ISSUE: Prospective, randomized, controlled trials (RCTs) are considered the gold standard for evidence of clinical efficacy and are generally required for CMS coverage of wound healing therapeutics like cellular and/or tissue based products (CTPs). However, wound healing RCTs may not be generalizable because they exclude subjects with the serious co-morbid diseases common to patients with chronic wounds, they invariably target less severe wounds, are carried out over unrealistically short time frames, and fail to include patient centered outcomes. Furthermore, the rate at which new products come to market makes adequate comparative trials between biologicals improbable. Registry data derived from electronic health records may provide a way forward to identify the most cost effective interventions in real world scenarios, provide patient centered outcomes, facilitate low cost comparative effectiveness studies, and enable post marketing surveillance. However, debate persists regarding the best methodology for the use of registry data, and whether real world effectiveness data will ever be considered on par with RCTs due to the difficulty in controlling bias, missing data, and the challenges in creating comparative cohorts.  OVERVIEW: Chronic wounds like diabetic foot ulcers, venous leg ulcers and pressure ulcers costs  more than $50 billion dollars per year in direct (and indirect) medical costs and are a rapidly increasing healthcare burden. Research challenges include the heterogeneity of wounds, the many patient comorbid conditions that affect healing, and the wide range of treatments available (devices, pharmaceuticals, biologicals (e.g., cellular and/or tissue based products). The Meaningful Use requirement for clinicians to submit data to a specialty registry provides an opportunity to harness big data to drive wound care economic and outcomes research.