BACKGROUND: There has been a global upsurge of waterpipe (WP) smoking over the past several years. This can be attributed at least partly to various factors like lack of knowledge regarding its health effects, social acceptability, and intensive preventive programs focusing selectively on cigarettes smoking. PURPOSE: This study aimed to determine the prevalence and psychosocial determinants of WP smoking among secondary school adolescents in Al Hassa, Saudi Arabia, and also to assess their attitudes toward WPs smoking and knowledge regarding the related health effects. METHODS: Cross-sectional study included 1,652 students of both genders selected by multistage proportionate sampling method. Data collection was carried out using a self-administered anonymous Arabic version of the Global Youth Tobacco Survey, modified with items dedicated to WP smoking. Items to assess participants' knowledge about the health-related hazards and attitude towards WP were added. Patient Health Questionnaire was used to screen for the presence of anxiety and depressive disorders. RESULTS: Of the included adolescents, 358 (21.7%) were current smokers; cigarettes (46.1%), both cigarettes and WP (16.5%), and only WP (37.4%). Current WP users accounted for 193; 96.4% were males and 62.7% were ≥18 years of age. Outing, boredom, meeting friends, and family gatherings were the most frequently stated motives. WP users demonstrated a higher incidence of depressive and generalized anxiety disorders. Common assumptions regarding WP smoking included: WP smoking is less harmful than cigarettes and with no addictive property as stated by 47.8% and 65.9% of adolescents, respectively, harmful substances are purified through water filtration as believed by 59.2%, and it is more socially acceptable than cigarettes as agreed by 54.1%. Hierarchical regression analysis showed that male gender and increasing age of adolescents, WP smoking among close family and friends, and socializing motives were significant predictors for the current WP smoking state. CONCLUSION: Social acceptability, poor knowledge of WP health-related hazards, and socio-demographics are favoring the current increasing trend of WP use among adolescents in Al Hassa, Saudi Arabia.