Objectives. To test a tailored mobile health (i.e., mHealth) intervention for waterpipe tobacco cessation in young adults. Methods. From 2018 to 2020 at 2 US sites, we conducted a randomized trial with 349 waterpipe tobacco smokers aged 18 to 30 years randomized to control (no intervention), untailored, or tailored intervention arms. Intervention arms received a 6-week mHealth intervention conveying risks of waterpipe tobacco through text and images and strategies to enhance motivation and support quitting. The tailored intervention was personalized to baseline measures and intervention text message responses. Risk appraisals, motivation to quit, waterpipe smoking frequency, and cessation were assessed at 6 weeks, 3 months, and 6 months. Results. At 6 months, cessation was higher in the tailored (49%) than the control arm (29%; odds ratio = 2.4; 95% confidence interval = 1.3, 4.2) and smoking frequency was lower in the tailored (mean = 3.5 days) than the control arm (mean = 4.3 days; P = .006). At interim follow-ups, significant differences in other outcomes favored the tailored intervention. Conclusions. Tailored mobile messaging can help young adult waterpipe tobacco smokers quit. This scalable intervention is poised for population implementation.