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The aim of the study was to evaluate the prophylactic effect of Tafenoquine in healthy people and to assess the efficacy and safety of Tafenoquine in patients with malaria. A search was performed in PubMed and Cochrane for randomized controlled trials published until January 2, 2019. Study participants were healthy or patients who presented with malarial symptoms. The primary endpoints were clinical response rate, relapse-free, malaria during chemoprophylaxis, protective efficacy, incidence density, parasite clearance time, gametocyte clearance time, fever clearance time. Two reviewers independently involved in the study selection, data extraction and quality assessment. Statistical analysis was performed in the Review Manager 5.3 statistical software. We included 13 studies with 4860 patients for analysis. The pooled analyses reported that relapse was significantly (p<0.00005) in favour of the Tafenoquine 300mg plus Chloroquine compared to Chloroquine (RR 0.14, 95% CI 0.06 to 0.30, 3 trials, n= 126 patients,. The summary estimate reported the relapse-free outcome was in favor of Primaquine plus Chloroquine compared to the Tafenoquine 300mg plus Chloroquine (RR 1.15, 95% CI 1.00 to 1.33, 2 trials, n= 175 patients,. There was no significant difference in the risk of relapse and adverse events between the Tafenoquine and control group (Placebo, Primaquine, CQ+PQ). Tafenoquine 300mg plus Chloroquine has good efficacy in preventing relapses compared to the Chloroquine. However, adverse events are more with the Tafenoquine compared to the control. Further, highly powered randomized controlled clinical are needed to establish whether TQ is better in relapse prevention compared to PQ.