Two conditions that are highly stigmatized and that can be found in combination with one another are the stigma of substance use and HIV-related stigma. In this qualitative study, we investigated 15 substance users’ experiences surrounding their HIV status from their diagnosis to their disclosure decisions and the reactions from others. We explored the layering of substance use stigma with HIV-related stigma, the consequences of stigmatizing experiences, and coping strategies employed to deal with stigmatization. Motivations to disclose included being in poor health, having visible symptoms, others seeing HIV medication intake, poor access to medication without disclosure, being asked directly about one’s HIV status, emotional catharsis, believing that the target will maintain confidentiality, wanting to notify a partner of past or future risk, and disclosing as a stigma reduction effort. Reasons for concealment were needing time to process the diagnosis first, fear of negative reactions, previous negative experiences with disclosure, having been advised to conceal, not wanting to burden others, and believing that one’s HIV status 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 participants conveyed that substance use stigma is greater than HIV-related stigma. Emotional and social consequences were reported, along with a broad range of coping strategies. Implications for stigma reduction interventions are discussed.