OBJECTIVES Sickle-cell disease (SCD) patients are considered to be at high risk from open-heart surgery. This study assessed the role of a simple sickling-prevention protocol. METHODS Perioperative non-specific and SCD-specific morbidity and 30-day mortality are investigated in a retrospective cohort study on patients undergoing isolated mitral valve surgery. Patients with and without SCD were compared. In the SCD cohort, a bundle of interventions was applied to limit the risk of sickling: ‘on-demand’ transfusions to keep haemoglobin levels of around 7–8 g/dl, cardiopulmonary bypass (CPB) with higher blood flow and perfusion temperature, close monitoring of acid–base balance and oxygenation. RESULTS Twenty patients with and 40 patients without SCD were included. At baseline, only preoperative haemoglobin levels differed between cohorts (8.1 vs 11.8 g/dl, P CONCLUSIONS SCD patients may undergo open-heart surgery for mitral valve procedures with an acceptable risk profile. Simple but thoughtful perioperative management, embracing ‘on-demand’ transfusions and less-aggressive CPB cooling is feasible and probably efficacious.