Inpatient smokers with major depressive disorder (MDD) have high rates of relapse to smoking after hospital discharge. The risk of health consequences that may contribute to increased morbidity and mortality among this population underscores the need to develop a program for psychiatric inpatient cigarette smokers with MDD. Using a motivational interviewing (MI) intervention, we sought to facilitate engagement of smokers with elevated depression symptoms in an outpatient treatment with demonstrated efficacy for nicotine dependence. In Phase 1 of this program, we recruited 15 smokers with MDD who were receiving inpatient psychiatric services. This preliminary report focuses on the development of the intervention, and explores perceived barriers to quitting, methods of quitting, and interest in smoking cessation treatment following discharge from an inpatient stay. Understanding inpatient cigarette smokers’ interests in making changes in smoking, and in willingness to attempt cessation and engage in cessation treatment can inform efforts to curb smoking in this high-risk population.