<b>Objective</b>: Studies have demonstrated that supported housing is an effective intervention for individuals who are homeless and have a mental illness or substance use disorder. This study examined data from an experimental trial of the U.S. Department of Housing and Urban Development–Veterans Affairs Supported Housing (HUD-VASH) program to identify differences in the program’s impact on subgroups defined by sociodemographic or clinical characteristics. <b>Methods</b>: Data were analyzed from 259 male homeless veterans with substance abuse problems who were randomly assigned to HUD-VASH (intensive case management [ICM] plus rent subsidy vouchers), ICM only, or treatment as usual between June 1992 and December 1995. Four subgroups were defined: African American versus Caucasian, younger versus older than 42.3 years, co-occurring diagnoses of mental illness versus diagnosis of a substance use disorder only, and active versus less active substance use upon program entry. Mixed models were used to identify significant interactions between HUD-VASH assignment and each subgroup. <b>Results</b>: Compared with ICM alone, HUD-VASH was associated with more positive housing outcomes for Caucasians, veterans with co-occurring mental disorders, and veterans who were active substance users. HUD-VASH was associated with more positive socioclinical outcomes for African Americans. No differences were observed in housing or socioclinical outcomes as a function of age. <b>Conclusions</b>: Among homeless veterans with a substance use disorder, Caucasians and those with active substance use showed greater housing benefits than other veterans from HUD-VASH than from ICM alone. African Americans showed greater socioclinical benefit than Caucasians from HUD-VASH versus ICM. Interaction analysis deserves further study.