OBJECTIVE Prescription to over-the-counter (OTC) drug switches are increasingly common. Yet little is known about how the public uses these reclassified products. Histamine2-receptor antagonists (H2RAs) are popular examples, although they may be supplanted by OTC proton pump inhibitors (PPIs). We examined the extent to which consumers substitute OTC H2RAs for physician care and/or engage in off-label use of these medications. METHODS Self-administered anonymous survey of 1,116 adult OTC H2RA consumers in a random sample of 20 Los Angeles pharmacies from a major retail chain. Off-label use was defined by FDA warning label (e.g., bloody stools, dysphagia). Substitution was defined by intent to use H2RA instead of going to a physician. RESULTS Forty-six percent engaged in off-label use of OTC H2RAs. Off-label use was independently associated with lower income, substitution for physician care, prior gastrointestinal disease, and past prescription H2RA use. Thirty-four percent substituted OTC H2RA use for physician care, and 54% of these met the criteria for off-label use. Substitution was associated with lack of health insurance, lack of time to see a physician, the belief that OTC H2RA was cheaper than clinic visits, and nonwhite race. CONCLUSIONS Almost one-half of adult consumers reported using OTC H2RAs in a manner inconsistent with FDA labeling, and this off-label use was associated with substitution for physician care. Traditionally vulnerable populations were more prone to off-label use and to substituting H2RAs for physician care. Further studies are needed to assess patient outcomes, identify remedies, and explore implications for the reclassification of PPIs.