Background: Given the increase in life expectancy among HIV-positive individuals attributable to antiretroviral therapies, cigarette smoking now represents one of the most salient health risks confronting the HIV-positive population. Despite this risk, very few efforts to date have been made to target persons living with HIV for smoking cessation treatment, and no efforts have been made to explore the role of cognitions and HIV disease events/stages on smoking outcomes. The purpose of the study, Project STATE (Study of Tobacco Attitudes and Teachable Events), is to prospectively examine the relationship between HIV events/stages, perceived impact of HIV disease, attitudes about cigarette smoking, and smoking behaviors. Methods/Design. This study employs a prospective design. Patients are recruited at the time of their first physician visit at a large inner city HIV-clinic - Thomas Street Health Center (TSHC). Consenting participants then complete a baseline assessment. All participants are offered standard care smoking cessation treatment. Follow-up assessments are completed on four subsequent occasions: 3, 6, 9, and 12 months post-baseline. These follow-up assessments are scheduled to coincide with routine clinic appointments with their TSHC physicians. In addition, each participant is given a prepaid cell phone at the time of enrollment and asked to complete brief phone assessments weekly for the first three months of the study period. Discussion. By evaluating events/stages of HIV disease as potential teaching moments for smoking cessation, findings from this study could be used to develop treatments tailored to an individual's stage of HIV disease. This study design will enable us to carefully track changes in smoking behavior over time, and to link these changes to both the course of HIV disease and/or to the participant's' perceived impact of HIV. By identifying optimal time points for intervention, the findings from this study will have the potential to maximize the efficiency and efficacy of cessation treatments delivered in resource-limited settings. In addition, the findings will be instrumental in identifying specific constructs that should be targeted for intervention and will provide a strong foundation for the development of future cessation interventions targeting smokers living with HIV/AIDS. © 2014 Vidrine et al.; licensee BioMed Central Ltd.