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Background and Objectives: The donor medical questionnaire identifies a blood donor's history of known blood safety risks. Current Australian, Canadian, European and USA legislation temporarily defers blood donors who received different percutaneous needle treatments (i.e. tattooing, acupuncture and piercing) from blood donation. This systematic review aimed to scientifically underpin these deferrals by identifying the best available evidence on the association between percutaneous needle treatments and the risk of transfusion-transmissible infections (TTIs)., Materials and Methods: Studies from three databases investigating the link between percutaneous needle treatments and TTIs (HBV, HCV and HIV infection) in blood donors were retained and assessed on eligibility by two reviewers independently. The association between percutaneous needle treatments and TTIs was expressed by conducting meta-analyses and calculating pooled effect measures (odds ratios (ORs) and 95% CIs). The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the quality of evidence., Results: We identified 1242 references and finally included 21 observational studies. Twenty studies assessed the link between percutaneous needle treatments and HCV infection and found that blood donors receiving these treatments had an increased risk of HCV infection (tattooing: pooled OR 5·28, 95% CI [4·33, 6·44], P < 0·00001 (low-quality evidence); acupuncture: pooled OR 1·56, 95% CI [1·17, 2·08], P = 0·03 (very low-quality evidence); and piercing: pooled OR 3·25, 95% CI [1·68, 6·30], P = 0·0005 (low-quality evidence))., Conclusion: Percutaneous needle treatments may be associated with an increased HCV infection risk. Further high-quality studies are required to formulate stronger evidence-based recommendations on percutaneous needle treatments as a blood donor deferral criterion., (© 2019 International Society of Blood Transfusion.)