Cigarette smoking has profound negative effects on oral health. Smoking cessation decreases the incidence and progression of oral health problems. Most smokers attempt to quit, but the majority of quit attempts are unaided by smoking cessation medications and end in relapse. The American Dental Hygienists Association recommends that all oral health professionals Ask patients if they smoke, Advise smokers to quit, and Refer smokers to quitlines for counseling (Ask-Advise-Refer; AAR). AAR connects patients directly to counseling but not to medication, which can double cessation rates independent of counseling. Indeed, few dentists prescribe cessation medications. Failure to connect smokers to medication is a critical missed opportunity to prevent disease and save lives. Nicotine Replacement Therapy Sampling (NRTS) refers to providing all smokers, regardless of current interest in quitting, with free samples of over-the-counter NRT products and brief use instructions. NRTS has been shown to increase quit attempts and smoking abstinence rates. Dental settings are an ideal fit for NRTS because NRTS could easily be combined with AAR and providing samples of oral care products is routine and universal in dental care settings. The proposed UG3/UH3 project will test the effectiveness of NRTS in dental practices. In the 2-year Clinical Trial Planning Phase (UG3), we will complete all required milestones to establish feasibility and acceptability of study protocols and prepare for the 3-year Clinical Trial Implementation Phase (UH3). UG3 activities will include stakeholder interviews to evaluate initial acceptability and feasibility of proposed study interventions and procedures, pilot testing, protocol refinement, and recruitment of practitioners for the UH3 trial. In the UH3 trial, we propose to conduct a cluster randomized, hybrid type 1 implementation-effectiveness trial comparing AAR + NRTS (NRTS) to enhanced usual care (ET; AAR + electric toothbrush; N = 50 practitioners, limited to 1 per practice; N = 1200 patients) recruited from the Northeast and Midwest Regions of the National Dental Practice-Based Research Network. Study interventions will be delivered within the practices by trained practice staff. Our central hypothesis is that NRTS will produce greater abstinence rates than ET. Our primary outcome will be biologically verified, 7-day point prevalence abstinence at 6-months post-intervention. We also predict that compared to ET, NRTS will increase rates of quit attempts, reduce smoking heaviness, and increase NRT utilization. We will conduct a multi-stakeholder process evaluation of the feasibility and acceptability of the NRTS intervention and a cost-effectiveness analysis to aid future implementation efforts. Overall, we expect that, as a result of this project, we will establish the feasibility, acceptability, and effectiveness of NRTS in dental practices and determine that NRTS has high potential for translation to clinical practice.