Objective. This is an interim analysis of a prospective, parallel, randomized, single-center study involving 16 subjects in an outpatient wound care center setting, and the objective of the study is to evaluate the safety and effectiveness of a hyaluronic acid extracellular matrix (HA) for the treatment of chronic venous leg ulcers (VLUs). Materials and Methods. Each subject with a VLU was randomized (1:1) to receive either HA plus compression with a multilayer compression bandage (MLC) or standard care consisting of a nonadherent primary dressing plus a MLC (control). All wounds were VLUs (confirmed by duplex imaging) and all had adequate arterial circulation (ankle-brachial index > 0.75). All VLUs had a history of not healing > 6 months, and all were in the lower leg (between the midcalf and below malleoli). Traditional MLC with a short stretch and elastic cohesive bandage was used in all patients. The primary endpoint was incidence of wound healing at 12 and 16 weeks, and secondary endpoints were time to healing and ulcer recurrence. Wound evaluations were performed weekly and wound surface area was measured by photodigital planimetry. Results. The incidence of wound healing at 12 weeks was 66.6% for the HA group and 14.2% for the control (P = .066). At week 16, 87.5% were healed in the HA group compared with 42.8% in the control (P = .059). The mean time to healing in the HA-treated group was 41 days compared with 104 days in the control (P = .029). Conclusion. Results of this interim analysis indicate that continuation of the present study is warranted and provides a more reliable power calculation forecasting that the inclusion of 50 to 60 subjects would be needed to achieve the statistical goal (P < .05) related to the primary endpoint.