To quantify the evidence for infection-control interventions among high-risk cancer patients and haematopoietic stem-cell recipients, we did a systematic review of prospective comparative studies. Protective isolation, including air quality control, prophylactic antibiotics, and barrier isolation (29 studies), brought about a significant reduction in all-cause mortality: risk ratio 0.60 (95% CI 0.50-0.72) at 30 days (number needed to treat [NNT] 20 [95% CI 14-33]) and 0.86 (95% CI 0.81-0.91) at the longest follow-up (up to 3 years; NNT 12 [95% CI 9-20]). Inclusion of prophylactic antibiotics in the intervention was necessary to show the effect on mortality. The combined intervention reduced bacteraemia, and Gram-negative, Gram-positive, and Candida spp infections. Mould infections were not significantly reduced. 11 non-randomised prospective studies assessed inpatient versus outpatient management after autologous stem-cell transplantation. All-cause mortality was lower among outpatients: risk ratio 0.72 [95% CI 0.55-0.95]. We conclude that prophylactic antibiotics are the most effective treatment within the protective environment. Randomised trials on outpatient management of haematological cancer patients are needed.