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Objectives: Manuka honey attacks biofilms, which contribute to bacterial persistence in cystic fibrosis sinusitis. The primary objective was to determine feasibility of investigating manuka honey as an irrigation treatment for cystic fibrosis sinusitis and secondarily to assess the treatment's preliminary effectiveness. Design: Prospective, single‐blinded (clinician only), randomised, parallel two‐arm pilot trial. Setting: Tertiary rhinology clinic. Participants: Subjects had recalcitrant cystic fibrosis sinusitis and previous sinus surgery. They received manuka honey or saline sinus irrigations twice daily for 30 days. Main Outcome Measures: Main outcomes were recruitment/retention rates and tolerability. Preliminary effectiveness was assessed based on quality‐of‐life Sinonasal Outcome Test‐22 and Lund‐Kennedy endoscopic change scores and post‐treatment culture negativity. Results: Over 10 months, 13 subjects were enrolled, and 77% (10/13) were included in the analysis. Manuka honey irrigations were well‐tolerated. The quality‐of‐life change score was clinically significant for manuka honey (−9 [−14,−6]) but not saline (−5 [−9,−1]), although the difference was not statistically significant (P =.29). Lund‐Kennedy endoscopic change score was significantly better for manuka honey (−3 [−5,−3]) versus saline (0 [0,0]) (P =.006). There was no difference in post‐treatment culture negativity between manuka honey (1/5, 20%) and saline (0/5, 0%) (P = 1.00). Conclusions: Manuka honey irrigations were well tolerated, and retention rates were high. Preliminary data showed that manuka honey achieved a clinically important difference in quality‐of‐life score and a significantly better endoscopic outcome. Microbiological control was difficult to achieve. A future definitive trial would require multi‐institutional recruitment. [ABSTRACT FROM AUTHOR]