White people who are over 50 and have lower incomes are the hardest hit by the spike, said the findings in the journal Health Affairs.
In 2000, less than one half of one per cent (.43) of opioid-driven hospitalisations resulted in death, compared to 2.02 per cent in 2014, said the study, led by Harvard University researchers.
"More than 35,000 people died from heroin and synthetic opioid overdoses last year," said study senior author Zirui Song, an assistant professor of health care policy at Harvard Medical School.
The rate of opioid-driven hospitalisations has remained relatively stable, but "patients are increasingly likely to be hospitalised for more deadly conditions such as opioid poisoning or heroin poisoning," said the report.
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Prior to 2000, most opioid hospitalisations were for opioid dependence and abuse.
Death rates are unchanged among people admitted to hospital for other kinds of non-opioid drugs.
The study is the first to focus on patients whose primary diagnosis was related to opioids.
"These results are just scratching the surface of what health professionals and policymakers could use to help patients and the public, and the picture they paint is concerning," said Song.
"As the United States combats the opioid epidemic, efforts to help hospitals respond to the increasing severity of opioid intoxication are acutely needed, especially in vulnerable and disabled populations.