Background: Waterpipe tobacco smoking rates in the Eastern Mediterranean region are some of the highest worldwide, especially among young people. This study aimed to improve our knowledge of the policy-relevant context of waterpipe smoking among six countries in the Eastern Mediterranean region. Methods: In-depth interviews were conducted in Bahrain, Egypt, Jordan, Lebanon, Palestine, and the United Arab Emirates. Participants were young adult university students (18-29 years) from both genders who had ever smoked the waterpipe, recruited from universities participating in this study. Directed content analysis was used to analyze the transcripts. Results: A total of 53 in-depth interviews were conducted in Arabic in 2016. Findings were organized around 5 themes: waterpipe product characteristics; patterns of waterpipe smoking; the waterpipe café setting; perceived health consequences; and health warning labels. Waterpipe smoking was commonly perceived as a safe alternative to cigarettes. Waterpipe tobacco was reported to be widely accessible and affordable to young participants. There is a lack of knowledge among waterpipe smokers about the associated health effects. Warning labels are effective at communicating health risks associated with waterpipe smoking. Conclusions: Regulatory frameworks for waterpipe tobacco smoking should be developed and enforced, including waterpipe-specific health warning labels that elucidate the harmful effects of waterpipe smoking.