Many Bostonians and fans of the marathon, the world's oldest annual meet, see Monday as a chance to defy terrorism.
This year, organizers widened the number of entries from 27,000 last year to 36,000, close to the record 38,708 who ran in 1996 on the centenary of the race.
There will be more than 35,660 runners, 5,330 of whom come from 70 countries outside the United States.
Last year's win by Ethiopia's Lelisa Desisa passed almost unnoticed.
He returns to Boston, one of the six biggest foot races in the world and part of the prestigious World Marathon Majors circuit.
The 24-year-old has met several victims of the attacks calling them "an inspiration" and has said he will be running again to show that he has no fear.
Several former winners are also taking part on Monday, including America's Joan Benoit Samuelson, who won in 1979 and 1983, and Amby Burfoot (1968), who last year failed to complete the race in the wake of the attacks.
Josef Klobusnik, a Slovakian living in Minnesota, said he was still hurting because of what happened.
"Last year was very painful for me, I had a lot of friends here," he told AFP.
On Tuesday, Boston paid emotional homage to the victims, survivors and first responders, united in their determination to conquer the fear of last year.
Vice President Joe Biden led the tribute, calling the survivors an inspiration to people all over the world.
Monday's marathon, Biden said, would send a message to the rest of the world and "to the terrorists that we will never yield, we will never cower."
But in the evening, hundreds of people were evacuated and a 25-year-old man detained for questioning over two suspicious backpacks found near the finish line.
Authorities have announced an economic impact of $175.8 million in the Boston region, the highest in the history of the marathon.
The record so far was the 1996 rendition of the race, which generated $172 million.
The Tsarnaev brothers were identified as perpetrators of the attacks within days thanks to footage from cameras and thousands of photographs.
Tamerlan, 26, was shot by police on April 19, 2013, after killing an officer and Dzhokhar, now 20, was captured and stands accused of 30 federal charges. He is awaiting trial and could face the death penalty if convicted.