Introduction: Although homeless individuals smoke at an alarmingly high rate, few smoking cessation clinical trials have focused on this vulnerable population. Little is known about recruitment efforts and suitable eligibility criteria for tobacco control research in homeless populations. Methods: The aim of this article is to describe the recruitment, eligibility, and enrollment of homeless smokers who participated in the Power to Quit smoking study, a randomized smoking cessation clinical trial funded by the National Institutes of Health. The study compared motivational interviewing and standard counseling while participants received an 8-week treatment of the nicotine patch. Results: Working with local emergency shelters, a total of 839 adult smokers were screened for study eligibility, 580 of whom (69.1%) met eligibility criteria. Of those eligible, 430 (74.1%) returned for randomization. Those who returned for randomization were older and more likely to have a phone number compared with eligible participants not enrolled. The most common reasons for exclusion included exhaled carbon monoxide levels less than or equal to 5 parts per million (indicating nonsmoking status), use of smoking cessation aid during the past 30 days, and not meeting the study definition of homelessness. Conclusion: Knowledge of these factors may help researchers tailor criteria that accurately identify and include homeless smokers in future research.