Although a considerable body of evidence supports telephone quit lines for smoking cessation, much less is known about the effectiveness of proactive Telephone Counseling with smokeless tobacco (ST) users. We conducted a randomized controlled trial comparing telephone counseling with the distribution of a self-help manual for ST cessation. We recruited 406 adult ST users throughout the state of Minnesota and randomized them to receive either: (a) a self-help manual (Manual only) or (b) a self-help manual plus proactive telephone-based cessation counseling (Telephone Counseling). The telephone-based treatment included up to four calls in support of quitting, and personalized various cognitive and behavioral strategies that are generally considered effective in tobacco cessation (such as setting a quit date, examining patterns of use, developing stress reduction skills, avoiding known triggers to use). Participants were surveyed by phone at 3 and 6 months to assess both point prevalence and continued abstinence. Prolonged abstinence from all tobacco was 6.8% and 30.9% (p < .001) at 3 months and 9.8% and 30.9% (p < .001) at 6 months in Manual only and telephone counseling, respectively. We found older age, lower dependency, and increased readiness predicted quitting success. Proactive telephone-based counseling is an effective strategy for improving cessation rates among ST users. Future research should determine the components contributing to the intervention success.