Cardiovascular disease (CVD) in the United States disproportionally affects people who are homeless. This disparity is a critical concern that needs to be addressed to improve the health of individuals who are homeless. The connections between a history of homelessness, i.e., its duration and frequency, and CVD risk are not well understood. The present study sought to investigate how a history of homelessness is correlated with CVD risk factors in a sample of homeless persons in the Deep South. This study recruited participants who were homeless from two local adult homeless shelters in Birmingham, AL. Participants (n = 61) underwent interviews, physical measurements, and a capillary blood draw. Their mean age was 47 years, and 82% were men. Results showed the duration of homelessness was positively associated with several CVD risk factors (diabetes mellitus, total cholesterol, and low-density lipoprotein). However, there was no significant association between frequency of homelessness and any CVD risk factors. To get the more accurate estimate of CVD risk in this population, future research should incorporate additional risk factors related to homelessness and seek to develop a robust strategy to collect an accurate history of homelessness.