While the use of smokeless tobacco products has increased, there has been a paucity of research evaluating interventions to help users quit. This study is the first large-scale randomized trial evaluating two levels of self-help cessation intervention with adult smokeless tobacco (SLT) users. Smokeless users in five Northwest states were recruited to call a toll-free number and 1069 users were randomized to receive one of two interventions, Manual Only (MAN) or Assisted Self-Help (ASH), who received a video and two support phone calls in addition to the manual. The study demonstrated that low-cost minimal interventions done by mail and phone can help a sizable proportion of SLT users quit both SLT and all tobacco use. Follow-up data at 6 months showed that subjects in the ASH condition had a significantly higher quit rate for both smokeless (23.4% vs. 18.4%, p < 0.05) and all tobacco use (21.1% vs. 16.5%, p < 0.05), using an intent-to-treat model. Further analysis revealed that use of the recommended cessation procedures mediated the effect of intervention condition on outcomes. This may be the result of phone counselors getting subjects to carry out behavioral cessation procedures. Public health implications for this intervention are discussed.