The biological effects of smoking water pipe on haemostasis and the eicosanoid system is unknown. Water pipe smoking is familiar to approximately 1 billion people around the world. Considering this quite impressive number, we investigated the potential effect of smoking the Narghile on oxidation injury by monitoring parameters of the (iso)eicosanoid system. Patients were allowed to smoke a water pipe once daily for 14 days. Blood was drawn from 7 healthy adult non-cigarette smoking male volunteers before and immediately after the first smoking of the water pipe and additionally after 6 hours. One and 2 weeks thereafter, blood was drawn again before and after smoking. A total of 7 blood samples was drawn during the study, and parameters of in vivo oxidation injury (8-epi-PGF2alpha, malondialdehyde [MDA]) and haemostasis (11-dehydro-thromboxane B2 [11-DH-TXB2]) were investigated. A single smoking session increased oxidation injury (8-epi-PGF2alpha: p=0.03; MDA: p=0.001) and 11-DH-TXB2 (p=0.00003) significantly, and repeated daily smoking induced a persistent long-lasting oxidation injury reflected by elevated prevalues but a smaller response to the actual water pipe smoke. These findings indicate a significant increase of in vivo oxidative stress by regular water pipe smoking.