The railroad, with headquarters in Fort Worth, Texas, and owned by Berkshire Hathaway, burns 1.3 billion gallons of diesel per year.
"This could be a transformational event for our railroad," BNSF Chief Executive Matt Rose told The Wall Street Journal.
A shift to natural gas would "rank right up there" with railroads' historic transition away from steam engines last century, he said.
BNSF said it will test six locomotives modified for LNG use: three from Caterpillar and three made by General Electric. The company expects to make a decision in 2014 on whether it will begin to switch its fleet of more than 6,900 locomotives to natural gas.
"It comes down to the spread relationship between LNG and diesel," Rose said, in announcing the experiment at the IHS CERAWeek energy conference Houston this week.
"Once you get that in your head you can make that decision pretty quickly."
Government statistics indicate that diesel fuel cost an average of $3.97 a gallon last year. The equivalent amount of energy in natural gas cost 48 cents at industrial prices.
Canadian National Railway, the largest in that country, began a trial with natural gas last September.
While BNSF had tested LNG in the late 19802, LNG was too expensive then.
The railway already has a major role in the oil sector. In February, it transported more than 571,000 barrels of oil per day in February, an amount that is expected to grow that rate to more than 700,000 barrels per day by the end of this year.
Rose, however, acknowledged there will be challenges with the switch to LNG, saying, "While there are daunting technical and regulatory challenges still to be faced, this pilot project is an important first step that will allow BNSF to evaluate the technical and economic viability of the use of liquefied natural gas in through-freight service, potentially reducing fuel costs and greenhouse gas emissions, thereby providing environmental and energy security benefits to our nation."
Rose said that preliminary tests indicate that LNG-powered trains can travel further than diesel trains before needing to refuel and have comparable towing power.
Although railways account for just 6 percent of diesel burned in the United States, BNSF's move calls attention to the possibilities of LNG as a transport fuel.
"This is the kind of change that gets people thinking," Kevin Book, an energy-industry consultant was quoted as saying by the Journal. "It will answer the question that everyone is wondering: Is there a future for LNG transportation for freight hauling?"