IMPORTANCE Several national health care-based smoking cessation initiatives have been recommended to facilitate the delivery of evidence-based treatments, such as quitline (telephone-based tobacco cessation services) assistance. The most notable examples are the 5 As (Ask, Advise, Assess, Assist, Arrange) and Ask. Advise. Refer. (AAR) programs. Unfortunately, rates of primary care referrals to quitlines are low, and most referred smokers fail to call for assistance. OBJECTIVE To evaluate a new approach-Ask-Advise-Connect (AAC)-designed to address barriers to linking smokers with treatment. DESIGN A pair-matched, 2-treatment-arm, group-randomized design in 10 family practice clinics in a single metropolitan area. Five clinics were randomized to the AAC (intervention) and 5 to the AAR (control) conditions. In both conditions, clinic staff were trained to assess and record the smoking status of all patients at all visits in the electronic health record, and smokers were given brief advice to quit. In the AAC clinics, the names and telephone numbers of smokers who agreed to be connected were sent electronically to the quitline daily, and patients were called proactively by the quitline within 48 hours. In the AAR clinics, smokers were offered a quitline referral card and encouraged to call on their own. All data were collected from February 8 through December 27, 2011. SETTING Ten clinics in Houston, Texas. PARTICIPANTS Smoking status assessments were completed for 42 277 patients; 2052 unique smokers were identified at AAC clinics, and 1611 smokers were identified at AAR clinics. INTERVENTIONS Linking smokers with quitline-delivered treatment. MAIN OUTCOME MEASURE Impact was based on the RE-AIM (Reach, Efficacy, Adoption, Implementation, and Maintenance) conceptual framework and defined as the proportion of all identified smokers who enrolled in treatment. RESULTS In the AAC clinics, 7.8% of all identified smokers enrolled in treatment vs 0.6% in the AAR clinics (t4 = 9.19 [P < .001]; odds ratio, 11.60 [95% CI, 5.53-24.32]), a 13-fold increase in the proportion of smokers enrolling in treatment. CONCLUSIONS AND RELEVANCE The system changes implemented in the AAC approach could be adopted broadly by other health care systems and have tremendous potential to reduce tobacco-related morbidity and mortality.