The objectives of this study were to estimate the prevalence of concurrent alcohol and substance use among patients living with HIV/HCV co-infection and to compare demographic and clinical characteristics of those with concurrent alcohol and substance to those with alcohol or substance use, and to those who were abstinent. We conducted an analysis of patient reported outcomes data of patients living with HIV/HCV co-infection (n = 327) who transitioned from primary care to sub-specialty care for evaluation of candidacy for HCV treatment at a university-affiliated HIV Clinic. The prevalence of self-reported concurrent alcohol and substance use was 33%. A higher proportion of those with concurrent alcohol and substance use were currently smoking tobacco, and those who were abstinent had higher ratings of health-related quality of life compared to those with alcohol or substance use. To reduce patients’ risk for progression to advanced stages of HIV, HCV, and liver-related disease due to continued alcohol and substance and tobacco use, social workers and other health care professionals are encouraged to develop and implement intervention strategies to assist patients living with HIV/HCV co-infection in efforts to achieve behavioral change.