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Summary We investigated the current role of interferon‐alpha (IFNα) in hairy cell leukaemia (HCL) in a retrospective analysis of patients with HCL. A cohort of 74 patients with HCL was divided in to three groups: (A) patients aged >65 years with first‐line treatment; (B) patients with comorbidities with first‐line treatment; (C) patients who were purine analogues resistant. In total, 94% achieved a response, with a complete response rate of 24%. After a median (range) follow‐up of 60 (7–236) months, 55 patients (78%) are still responding. The 5‐year progression‐free survival was 95%, 68%, and 96% in groups A, B and C respectively. A proportion of patients were monitored through their B‐Raf proto‐oncogene, serine/threonine kinase (BRAF)‐V600E status. IFNα remains a possible option in select patients with HCL, where minimal residual disease negativity is achievable.