Two conditions that are highly stigmatized are substance use and HIV. In this qualitative study, we investigated, through thematic analyses of verbatim transcripts, 15 substance users’ experiences with receiving their diagnosis, making disclosure decisions, and receiving and dealing with stigmatizing reactions. Motivations to disclose included being in poor health, having visible symptoms, others seeing HIV medication, poor medication access without disclosure, being asked directly, emotional catharsis, believing that the target will maintain confidentiality, notifying a partner of risk, and disclosing to reduce stigma. Reasons for concealment were needing time to process the diagnosis, fear of stigmatization, previous negative experiences with disclosure, being advised to conceal, not wanting to burden others, and believing that one’s HIV is irrelevant. Stigmatizing reactions from others included increased physical distance, excessive precautions, social avoidance, abandonment, rejection, exclusion, judgment, blame, name calling, gossip, denial, and requests to conceal status. Layered stigma was prevalent and substance use stigma was reported to be greater than HIV stigma. Emotional and social consequences were reported, as were a number of coping strategies. Findings are important input for stigma reduction