BACKGROUND Management of severely infected wounds is a formidable challenge. The pilot prospective cohort study is to investigate the influence of continuous topical irrigation (CTI) on the outcomes of severely infected wounds. METHODS This pilot study was performed on 17 patients with a single severely infected wound treated with CTI, compared with a control group of 15 patients treated with standard of care from January 2011-January 2013. Bates-Jensen wound assessment tool severity scores and the clinical outcomes were recorded. Profiles of cytokines and/or proteinase in wound fluid were quantified weekly. RESULTS Comparing with the control, the CTI-treated patients required fewer days for wound infection clearance (8 ± 2 versus 19 ± 5 d, P < 0.001), had wounds closed earlier (17 ± 4 versus 36 ± 7 d, P < 0.001), and had fewer inhospital stay days (23 ± 5 versus 42 ± 8 d, P < 0.001). Bates-Jensen wound assessment tool severity scorings, proinflammatory cytokines (tumor necrosis factor-α, interleukin 1β, and interleukin 6), and matrix metalloproteinase-8 were significantly decreased in response to CTI. CONCLUSIONS This pilot study demonstrates that CTI improves severely infected wound healing through partly inhibiting proinflammatory cytokines and improving tissue regeneration.