Importance: Concerns that take-home naloxone (THN) training may lead to riskier drug use (as a form of overdose risk compensation) remain a substantial barrier to training implementation. However, there was limited good-quality evidence in a systematic review of the association between THN access and subsequent risk compensation behaviors.

Question: Do people who inject drugs increase their injecting frequency (a key marker of overdose risk) after take-home naloxone (THN) training and supply?

Findings: In this cohort study of 1328 people who inject drugs, no change in injecting frequency was observed after THN training.

Meaning: Findings of this study suggest that THN training was not associated with increased injecting frequency and should not be withheld due to concerns about overdose risk compensation and that advocacy for widespread availability and uptake of THN is needed to address unprecedented opioid-associated mortality.