Lay health advisers (LHAs) are increasingly used to deliver tobacco dependence treatment, especially with low-socioeconomic status (SES) populations. More information is needed about treatment adherence to help interpret mixed evidence of LHA intervention effectiveness. This study examined adherence to behavioral counseling and nicotine patches in an LHA intervention with 147 Ohio Appalachian female daily smokers. Participants were randomly selected from clinics and randomized to the intervention condition of a randomized controlled trial. Overall, 75.5% of participants received all seven planned LHA visits, 29.3% used patches for greater than 7 weeks and approximately half received high average ratings on participant responsiveness. Depressive symptoms and low nicotine dependence were associated with lower patch adherence while high poverty-to-income ratio was associated with high responsiveness. Compared with those with fewer visits, participants who received all visits were more likely to be abstinent (22.5 versus 2.8%, P = 0.026) or have attempted quitting (85.0 versus 47.4%, P = 0.009) at 3 months. High participant responsiveness was associated with 12-month abstinence. LHA interventions should focus on improving adherence to nicotine patches and managing depression because it is an independent risk factor for low adherence.