In recent years, the number of waterpipe smokers has increased substantially worldwide. Here, we present a study on the identification and quantification of seven carbonylic compounds including formaldehyde, acetaldehyde and acrolein in the mainstream smoke of the waterpipe. Smoking was conducted with a smoking machine, and carbonyls were scavenged from the smoke with two impingers containing an acidic solution of 2,4-dinitrophenylhydrazine. The derivatives were then analyzed by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). For instance, during one waterpipe smoking session, up to 111 ± 12 μg formaldehyde could be detected. This value is about 5 times higher when compared to one 2R4F reference cigarette. We also found a distinct filter effect of the bowl water for all carbonyls investigated. Our data further demonstrate that increasing amounts of humectants in the unburned tobacco lowers the temperature in the waterpipe head during smoking, thereby resulting in decreasing levels of carbonyls in the smoke produced. Altogether, considerable amounts of toxic carbonyls are present in the waterpipe smoke, thus conferring a health risk to waterpipe smokers.