The desire to engage in waterpipe tobacco smoking (WTS) may occur when smokers and nonsmokers conjure positive mental simulations of WTS. However, effects of these simulations on desire to smoke waterpipe tobacco and potential mediators are unexplored. This research addressed these effects among young adult waterpipe tobacco smokers and nonsmokers. Two online studies were conducted with adults ages 18-30. In Study 1, 200 smokers, 190 susceptible nonsmokers, and 182 nonsusceptible nonsmokers were randomized to mentally simulate or not WTS in the future. In Study 2, 234 smokers and 241 susceptible nonsmokers were randomized to four arms: no simulation or simulations that varied valence of experience (positive, negative or no valence provided). Main outcomes were immediate desire to smoke waterpipe tobacco, cognitive and affective attitudes, and perceived harms. In Study 1, mental simulations increased the desire to smoke waterpipe tobacco among smokers. In Study 2, asking participants to simulate WTS positively or with no valence instruction increased desire to smoke relative to negative valence instruction or no simulation. Negative simulations reduced perceived probability of smoking within a month compared to positive simulations. Effects on desire to engage in WTS were mediated by cognitive and affective attitudes among susceptible nonsmokers and by cognitive attitudes among smokers. These findings suggest that exploring when and how often mental simulations about WTS are evoked and their potency for promoting prevention and cessation of WTS merit further attention.