ABSTRACT: BACKGROUND:Cessation counseling and pharmacotherapy are recommended for hospitalized smokers, but better coordination between cessation counselors and providers might improve utilization of pharmacotherapy and enhance smoking cessation. OBJECTIVE:To compare smoking cessation counseling combined with care coordination post-hospitalization to counseling alone on uptake of pharmacotherapy and smoking cessation. DESIGN:Unblinded, randomized clinical trial PARTICIPANTS: Hospitalized smokers referred from primarily rural hospitals INTERVENTIONS: Counseling only (C) consisted of telephone counseling provided during the hospitalization and post-discharge. Counseling with care coordination (CCC) provided similar counseling supplemented by feedback to the smoker's health care team and help for the smoker in obtaining pharmacotherapy. At 6 months post-hospitalization, persistent smokers were re-engaged with either CCC or C. MAIN MEASURES:Utilization of pharmacotherapy and smoking cessation at 3, 6, and 12 months post-discharge. KEY RESULTS:Among 606 smokers randomized, 429 (70.8%) completed the 12-month assessment and 580 (95.7%) were included in the primary analysis. Use of any cessation pharmacotherapy between 0 and 6 months (55.2%) and between 6 and 12 months (47.1%) post-discharge was similar across treatment arms though use of prescription-only pharmacotherapy between months 6-12 was significantly higher in the CCC group (30.1%) compared with the C group (18.6%) (RR, 1.61 (95% CI, 1.08, 2.41)). Self-reported abstinence rates of 26.2%, 20.3%, and 23.4% at months 3, 6, and 12, respectively, were comparable across the two treatment arms. Of those smoking at month 6, 12.5% reported abstinence at month 12. Validated smoking cessation at 12 months was 19.3% versus 16.9% in the CCC and C groups, respectively (RR, 1.13 (95% CI, 0.80, 1.61)). CONCLUSION:Supplemental care coordination, provided by counselors outside of the health care team, failed to improve smoking cessation beyond that achieved by cessation counseling alone. Re-engagement of smokers 6 months post-discharge can lead to new quitters, at which time care coordination might facilitate use of prescription medications. TRIAL REGISTRATION:NCT01063972.