Background: The rate of smoking commercial tobacco products among American Indian youth is double the rate for white youth. Interventions are needed to reduce this disparity. Objective: To test the feasibility of a Web-based intervention to influence attitudes toward and intentions about smoking cigarettes among American Indian youth who attended a Native summer camp in the Northern Plains. Methods: The study website, the SmokingZine, was originally developed and tested in Canadian youth, then adapted to be appropriate for American Indian youth. We conducted a randomized controlled trial to test the influence of exposure to the adapted SmokingZine website on smoking attitudes and behaviors among American Indian youth 12–18 years of age. Participants assigned to the intervention group were given access to the website for 1 hour per day during their camp experience and asked to sign in to the site and use it. Control group participants were not given access to the site. Results: A total of 52% of intervention youth signed in to the website at least once. Among nonsmokers, intentions to try a cigarette in the intervention group declined from 16% to 0%, and increased from 8% to 25% in the control group (P < .05). Compared with the control group, youth in the intervention group were more likely to help others quit (21 percentage point change in intervention versus no change in control; P < .05) and had less positive attitudes about the drug effects of smoking (–0.19 change in intervention versus 0.67 in control; P < .05). Conclusions: These data indicate that SmokingZine needs more long-term, rigorous investigation as a way to keep American Indian youth from becoming regular smokers. Because the intervention group could use computers only 1 hour per day, increasing access might result in more visits and a greater effect of the website on smoking behaviors.