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Electronic Nicotine Delivery System (ENDS) use and Waterpipe Tobacco Smoking (WTS) are reported to be a growing strain of tobacco epidemic among youth in the Arab world. Therefore, we aimed to: (1) estimate the regional prevalence of ENDS use among youth in 7 Arab countries and, (2) to explore the bidirectional relationship between ENDS use and WTS among Arab adolescents. We analyzed data from the World Health Organization Global Youth Tobacco Survey (GYTS 2014–2018) of 18,536 schoolchildren aged 12–16 from Iraq, Mauritania, Morocco, Oman, Qatar, Tunisia, and Yemen. The weighted prevalence was calculated to generate nationally representative estimates. Adjusted multilevel logistic regression models were conducted to assess the association between ENDS use and WTS. The pooled weighted prevalence of ENDS use was 9.5%. Higher odds of ENDS use were significantly associated with WTS (AOR: 5.26, 95%CI: 4.28–6.46), smoking conventional cigarettes (AOR: 1.54, 95%CI: 1.23–1.94) and first tobacco use prior to the age of 12 (AOR: 1.40, 95%CI: 1.14–1.72). Females and children who were taught in school the dangers of tobacco had less odds of using ENDS. WTS was associated with increased odds of ENDS use by >5 folds, and vice versa. Tobacco consumption at age younger than 12 years was associated with higher odds of ENDS use, but less odds of WTS. Females and those who were taught in school the dangers of tobacco were less likely to report ENDS use. • The pooled prevalence of ENDS use among youth from Iraq, Mauritania, Morocco, Oman, Qatar, Tunisia, and Yemen was 9.5%. • Waterpipe smoking was associated with increased odds of reporting e-cigarettes use by >5 folds, and vice versa. • Females and children who were taught in school the dangers of tobacco had less odds of using e-cigarettes. [ABSTRACT FROM AUTHOR]