Obama administration officials said most of the 1.5 million boilers nationwide are not covered by the regulation since they are too small or emit too little pollution to warrant controls.
The changes will require pollution controls at about 2,300 of the largest and most polluting boilers nationwide, including those found at refineries and chemical plants. Those boilers will have three years to comply and could be granted a fourth year if they need to install pollution controls.
Another 197,000 smaller boilers would be able to meet the rule through routine tune-ups.
The EPA said it cut the cost of compliance by about $1.5 billion.
Republicans have opposed the environmental regulations as detrimental to business during tough economic times and unsuccessfully tried to slow down the new rules in Congress.
The EPA estimated that despite the flexibility and the decision to target the largest polluters, the rules will still provide significant health benefits. The new standards will prevent up to 8,100 premature deaths, 5,100 heart attacks and 52,000 asthma attacks, according to the agency.
EPA estimated that Americans would receive $13 to $29 in health benefits for every dollar spent to meet the final standards and lead to a small net increase in jobs.
Environmental groups said the rules were not as stringent as they had hoped but would help Americans breathe cleaner air. "These standards are a mixed bag," said John Walke, director of the Natural Resources Defense Council's Clean Air Program.
Industry groups said the regulations were still overly burdensome. Jay Timmons, president and CEO of the National Association of Manufacturers, said the rules were "far from being realistic" and accused the EPA of pushing "another costly and crippling regulation at a time when our economy is on the brink."
Industrial boilers burn coal and other fuels to generate steam and hot water for heat and electricity. After coal-fired power plants, boilers are the nation's second-largest source of mercury emissions, a potent neurotoxin. But boilers are among a handful of pollution sources that still have no standards for toxic emissions.