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Background Legionnaires’ Disease (LD) has been recognized as a significant source of morbidity and mortality in many hospitals worldwide. Legionella in the hospital water distribution system has been epidemiologically linked to hospital-acquired LD. Despite the several disinfection methods available the optimal method to control hospital-acquired LD has not been established yet. Objectives To assess the efficacy of interventions for preventing hospital-acquired LD in hospitalized patients at high risk of developing the disease and the effect on environmental colonization associated to the risk of developing hospital-acquired LD. Search Methods We searched The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library and MEDLINE (PubMed). We also handsearched the reference lists of all primary studies identified by the initial search. Selection Criteria All controlled studies investigating the efficacy of interventions for the prevention of hospital-acquired LD, in hospitalized patients at high-risk for developing LD, were eligible for inclusion. Data collection and analysis Two authors independently assessed the trials and extracted data. Data was analysed using statistical software, Review Manager 5.2. Results Three controlled trials, two assessing copper-silver ionization and one assessing ultraviolet light (UVL), met the inclusion criteria. The meta-analysis showed a significant benefit in using copper-silver ionization rather than no intervention for Legionella positivity in distal sites, with RR = 0.04 (95% CI Fixed Effects 0.001, 0.29). One study demonstrated benefit of UVL versus no intervention with a RR = 0.03 (95% CI 0.00, 0.41) for Legionella positivity in water samples. Authors’ conclusions Our review demonstrates that copper-silver ionization and UVL are beneficial, compared with no treatment, to prevent hospital-acquired LD. However the quality of the body of evidence identified does not allow a robust conclusion regarding the effectiveness of interventions for preventing hospital-acquired LD. Further research with well design and high quality studies is needed.