The Controlled Substances Act imposes a 20-year mandatory minimum sentence on a defendant who unlawfully distributes a Schedule I or II drug, when “death or serious bodily injury results from the use of such substance.” Banka, a long-time drug user, died following an extended drug binge. The day before, Banka smoked marijuana at a former roommate’s home. Banka stole oxycodone pills from the roommate and later crushed, cooked, and injected the oxycodone. Banka and his wife, Tammy Noragon Banka (Noragon), then met with D and purchased one gram of heroin from him. Banka immediately cooked and injected some of the heroin and, after returning home, injected more heroin between midnight and 1 a.m. Noragon went to sleep at around 5 a.m., shortly after witnessing Banka prepare another batch of heroin. When Noragon woke up a few hours later, Banka was dead in the bathroom. Noragon called 911. A search of the couple’s home and car turned up syringes, 0.59 grams of heroin, alprazolam and clonazepam tablets, oxycodone pills, a bottle of hydrocodone, and other drugs. D was indicted. Two medical experts testified regarding the cause of Banka’s death. Multiple drugs were present in Banka’s system at the time of his death. Dr. Schwilke could not say whether Banka would have lived had he not taken the heroin. Dr. Schwilke concluded that heroin “was a contributing factor” in Banka’s death since it interacted with the other drugs to cause “respiratory and/or central nervous system depression.” Dr. McLemore came to similar conclusions. She described the cause of death as “mixed drug intoxication” with heroin, oxycodone, alprazolam, and clonazepam all playing a “contributing” role. She could not say whether Banka would have lived had he not taken the heroin, but observed that Banka’s death would have been “very less likely.” D moved for an acquittal in that there was no proof of but-for causation. The court denied the motion. The court gave an instruction requiring the Government to prove that the heroin was a contributing cause of Joshua Banka’s death. D was convicted. The Court of Appeals affirmed. The Supreme Court granted certiorari.