In an analysis to be released on Monday, the Council of Economic Advisers says the figure is more than six times larger than the most recent estimate.
The council said a 2016 private study estimated that prescription opioid overdoes, abuse and dependence in the US in 2013 cost $US78.5 billion.
The council said its estimate is significantly larger because the epidemic has worsened, with overdose deaths doubling in the past decade, and that some previous studies didn't reflect the number of fatalities blamed on opioids.
The council also noted that previous studies had focused exclusively on prescription opioids, while its study also factors in illicit opioids, including heroin.
"Previous estimates of the economic cost of the opioid crisis greatly underestimate it by undervaluing the most important component of the loss - fatalities resulting from overdoses," said the report, which the White House released.
Last month at the White House, President Donald Trump declared opioid abuse a national public health emergency. Trump announced an advertising campaign to combat what he said is the worst drug crisis in the nation's history, but he did not direct any new federal funding toward the effort.
More than 64,000 Americans died from drug overdoses last year, most involving a prescription painkiller or an illicit opioid like heroin.
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