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Niacin (vitamin B3) is promoted for rapidly clearing the body of drugs of abuse, such as cocaine and cannabis, and is alleged to interfere with urine drug screening. We present 4 cases of such novel use associated with significant adverse effects. Two cases had isolated skin manifestations, whereas the other 2 presented with life-threatening manifestations, including nausea, vomiting, dizziness, hepatotoxicity, metabolic acidosis, and hypoglycemia evolving into hyperglycemia. One patient also had profound neutrophilia and QT_C-interval prolongation. All patients improved after cessation of the drug use and supportive treatment. Health care providers should be aware of these potential adverse effects of niacin and of the misguided use of this vitamin by patients seeking to interfere with urine drug screening.