- BACKGROUND: There is a need for a comprehensive and critical review of the literature to inform scientific debates about the public health effects of waterpipe smoking. The objective of this study was therefore to systematically review the medical literature for the effects of waterpipe tobacco smoking on health outcomes. METHODS: We conducted a systematic review using the Cochrane Collaboration methodology for conducting systematic reviews. We rated the quality of evidence for each outcome using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Twenty-four studies were eligible for this review. Based on the available evidence, waterpipe tobacco smoking was significantly associated with lung cancer [odds ratio (OR) = 2.12; 95% confidence interval (CI) 1.32-3.42], respiratory illness (OR = 2.3; 95% CI 1.1-5.1), low birth-weight (OR = 2.12; 95% CI 1.08-4.18) and periodontal disease (OR = 3-5). It was not significantly associated with bladder cancer (OR = 0.8; 95% CI 0.2-4.0), nasopharyngeal cancer (OR = 0.49; 95% CI 0.20-1.23), oesophageal cancer (OR = 1.85; 95% CI 0.95-3.58), oral dysplasia (OR = 8.33; 95% CI 0.78-9.47) or infertility (OR = 2.5; 95% CI 1.0-6.3) but the CIs did not exclude important associations. Smoking waterpipe in groups was not significantly associated with hepatitis C infection (OR = 0.98; 95% CI 0.80-1.21). The quality of evidence for the different outcomes varied from very low to low. CONCLUSION: Waterpipe tobacco smoking is possibly associated with a number of deleterious health outcomes. There is a need for high-quality studies to identify and quantify with confidence all the health effects of this form of smoking.