Open fractures are common and potentially devastating. Their treatment remains focused on early irrigation and debridement. The question of whether negative pressure wound therapy is helpful remains unclear. The authors performed a secondary analysis of patients from the FLOW Trial who had Gustilo II and III lower extremity fractures. A propensity score matching system was applied to assess the risk of developing deep infection. Health-Related Quality of Life was also measured on the Short Form-12 (SF-12) Physical Component Summary (PCS) and Mental Component Summary (MCS). 270 matched pairs were analyzed. Those treated with negative pressure wound therapy had significantly higher risk of deep infection at 12 months and poorer quality of life at 6 weeks, 6 months, and 12 months. Overall, negative pressure would therapy is not recommended for open fractures based on this secondary analysis of a large randomized controlled trial.