A total of 2,975 people died in Puerto Rico within six months as a result of Hurricane Maria, according to an independent investigation ordered by the US territory.
The findings issued by the Milken Institute School of Public Health at George Washington University contrast sharply with the official death toll of 64.
It is also about double the Puerto Rican government's previous interim estimate of 1,400.
Researchers said there was a 22% increase in the number of deaths from September 2017 to February 2018 compared with previous years.
They said the initial low counts came partly because doctors lacked training on how to certify deaths after a disaster.
They added that the elderly and impoverished were most at risk.
Lynn Goldman, dean of the institute, told reporters: "We are hopeful that the government will accept this as an official death toll."
The study noted that mortality in Puerto Rico had been slowly decreasing since 2010, but spiked after the Category 4 storm hit on September 20.
About 40% of Puerto Rico's 78 municipalities saw a significantly higher number of deaths in the six months after the storm compared with the previous two years, researchers said.
These municipalities were mostly in the island's north east and south west.
Researchers found that the risk of death was 45% higher for those in impoverished communities, and that men older than 65 saw a continuous elevated risk.
They also said physicians and others told them that Puerto Rico's government did not notify them about federal guidelines on how to document deaths related to a major disaster.
"Others expressed reluctance to relate deaths to hurricanes due to concern about the subjectivity of this determination and about liability," the report said.
Researchers said they took into account an 8% drop in Puerto Rico's population from September 2017 to mid-February 2018, when tens of thousands fled the damage left by the storm.