Abstract Risk factors of smoking, drug and alcohol abuse, obesity, and sedentary lifestyle were related to health problems of clients at a walk-in clinic for the homeless. The sample of 1252 clients was predominately male (91.4%) and multiethnic, with a majority (65%) age 18 to 40 years. Data on diagnoses of health-related conditions were collected from clinic charts, coded into ICD categories, analyzed for relationships of risk factors to health problems, and compared with categories of diagnoses in a matched national sample of ambulatory care visits. Findings indicate that a larger proportion of homeless suffered from health problems in 24 of 27 diagnostic categories than the nonhomeless. Most prevalent were respiratory, dermal conditions, injuries, and digestive problems, in that order. Risk factors of alcohol abuse, smoking, sedentary lifestyle, drug abuse, and obesity were predictive of health problems in 18 of the categories analyzed. The findings suggest that immediate interventions such as education and rehabilitation to reduce risk factors, and provision of facilities for personal hygiene and cleaning of clothing could reduce some of the health-related conditions in this population while longer-term solutions of housing and employment are sought. The analysis model developed here appears to be a useful way of comparing relative effects of risk factors as a basis for establishing priorities for interventions.