Malaria is the most common precipitating cause of crises in sickle cell disease in malaria-endemic countries. Health professionals often recommend life-long malaria chemoprophylaxis for people with sickle cell disease living in these areas. It is therefore important we have good evidence of benefit. To assess the effects of routine malaria chemoprophylaxis in people with sickle cell disease. We searched the Cochrane Infectious Diseases Group Specialized Register (January 2006), Cochrane Cystic Fibrosis and Genetic Disorders Group Specialized Register (July 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to January 2006), EMBASE (1974 to January 2006), LILACS (1982 to January 2006), and reference lists. We also contacted organizations and pharmaceutical companies. Randomized and quasi-randomized controlled trials comparing chemoprophylaxis with any antimalarial drug given for a minimum of three months compared with a placebo or no intervention. Two authors independently applied the inclusion criteria, assessed the risk of bias in the trials, and extracted data. Dichotomous data were analysed using risk ratios (RR) and presented with 95% confidence intervals (CI). Two trials with a total of 223 children with homozygous sickle cell disease met the inclusion criteria. A randomized controlled trial in Nigeria compared two different antimalarial drugs with a placebo, and reported that chemoprophylaxis reduced sickle cell crises (RR 0.17, 95% CI 0.04 to 0.83; 97 children), hospital admissions (RR 0.27, 95% CI 0.12 to 0.63; 97 participants), and blood transfusions (RR 0.16, 95% CI 0.05 to 0.56; 97 participants). A quasi-randomized controlled trial of 126 children in Uganda compared an antimalarial drug plus antibiotics with no antimalarial plus placebo. Chemoprophylaxis reduced the number of episodes of malaria and dactylitis, and increased mean haemoglobin values in this trial. It is beneficial to give routine malaria chemoprophylaxis in sickle cell disease in areas where malaria is endemic. 4 November 2019 Update pending New contributors needed The CIDG Editors are looking for contributors to update and maintain this Cochrane Review. Contact the CIDG Managing Editor for further information.