This study revised the search strategy and conducted an updated search of MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE in April 2017. The study also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for ongoing trials. Data concerning outcomes, details of the interventions, and other study characteristics were extracted by two independent authors using a standardized data extraction form. Relative risk with a 95% confidence interval (CI) was used as the measure of effect. 12 randomized controlled trials that meet the criteria for the review were identified. Six were ongoing trials, four had been completed and two had been terminated early. Six studies with a total of 9849 participants provided data for this review. The trials evaluated the following: daily oral tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) versus placebo; TDF versus placebo and daily TDF- FTC versus intermittent TDF-FTC. One of the trials had three study arms: TDF, TDF-FTC and placebo arm. The studies were carried out amongst different risk groups, including HIV-uninfected men who have sex with men, serodiscordant couples and other high-risk men and women.