We assessed the ability of high-risk criteria developed by Boston Health Care for the Homeless Program to identify increased mortality during a 10-year cohort study (January 2000-December 2009) of 445 unsheltered adults. To qualify as high-risk for mortality, an individual slept unsheltered for six consecutive months or longer plus had one or more of the following characteristics: tri-morbidity, defined as co-occurring medical, psychiatric, and addiction diagnoses; one or more inpatient or respite admissions; three or more emergency department visits; 60 years old or older; HIV/AIDS; cirrhosis; renal failure; frostbite, hypothermia, or immersion foot. A total of 119 (26.7%) individuals met the high-risk criteria. The remaining 326 individuals in the cohort were considered lowerrisk. During the study, 134 deaths occurred; 52 (38.8%) were among high-risk individuals. Compared with sheltered individuals, the age-standardized mortality ratio for the high-risk group was 4.0 (95% confidence interval 3.0, 5.2) times higher and for the lower-risk group was 2.2 (1.8, 2.8) times higher. The hazard ratio, a measure of survival, for the high-risk group was 1.7 (1.2, 2.4) times that of the lower-risk group. High-risk criteria predicted an increased likelihood of mortality among unsheltered individuals. The lower-risk group also had high mortality rates compared with sheltered individuals.