Importance: In 2021, the state of Rhode Island distributed 10 000 additional naloxone kits compared with the prior year through partnerships with community-based organizations.

Question: What community-based naloxone distribution strategies would be the most effective and efficient in preventing opioid overdose deaths?

Findings: In this decision analytical model study evaluating the distribution of 10 000 additional naloxone kits annually in Rhode Island, the strategy focusing on distribution of naloxone according to geographic need to people who inject drugs resulted in the best outcomes at the lowest cost, averting an estimated 25.3% of opioid overdose deaths at an incremental cost of $27 312 per opioid overdose death averted.

Meaning: This study suggests that expanding naloxone distribution to people at highest risk for opioid overdose should be prioritized and that redirecting spatial distribution of naloxone to areas with the greatest need will improve both effectiveness and efficiency and reduce geospatial health inequality.