Overdose is the leading cause of premature mortality among heroin users. We examine whether the provision of regulated and quality-controlled heroin to users in specified doses would reduce heroin overdose rates. We also address this in the context of the epidemic of prescription opioid use and deaths seen in recent years in the United States and internationally. We explore the extent to which any change in legal access to heroin would affect overdose rates, and note that this depends upon the validity of the two main assumptions that variations in illicit drug purity and/or the presence of drug contaminants are major causes of overdose. Toxicological and demographic data from studies of heroin overdose deaths do not support these assumptions. The surge in the use of pharmaceutical opioids provides an example of the legal delivery of opioids of known dosage and free of contaminants, where overdose deaths can be examined to test these assumptions. Rates of fatal opioid overdose have escalated, with increased rates of prescribing of pharmaceutical opioids. On the basis of the experience with prescription opioids, unregulated legal heroin access would not reduce overdose rates.