OBJECTIVE: Waterpipe tobacco smoking (WTS) is an emerging trend worldwide. To inform public health policy and educational programming, we systematically reviewed the biomedical literature to compute the inhaled smoke volume, nicotine, tar, and carbon monoxide (CO) associated with a single WTS session and a single cigarette. METHODS: We searched seven biomedical bibliographic databases for controlled laboratory or natural environment studies designed to mimic human tobacco consumption. Included studies quantified the mainstream smoke of a single cigarette and/or single WTS session for smoke volume, nicotine, tar, and/or CO. We conducted meta-analyses to calculate summary estimates for the inhalation of each unique substance for each mode of tobacco consumption. We assessed between-study heterogeneity using chi-squared and I-squared statistics. RESULTS: Sufficient data from 17 studies were available to derive pooled estimates for inhalation of each exposure via each smoking method. Two researchers working independently abstracted measurement of smoke volume in liters, and nicotine, tar, and CO in milligrams. All numbers included in meta-analyses matched precisely between the two researchers (100% agreement, Cohen's k=1.00). Whereas one WTS session was associated with 74.1 liters of smoke inhalation (95% confidence interval [CI] 38.2, 110.0), one cigarette was associated with 0.6 liters of smoke (95% CI 0.5, 0.7). One WTS session was also associated with higher levels of nicotine, tar, and CO. CONCLUSIONS: One WTS session consistently exposed users to larger smoke volumes and higher levels of tobacco toxicants compared with one cigarette. These computed estimates may be valuable to emphasize in prevention programming.