Castroneves was chasing a record-tying fourth Indy win, and a mind-boggling 16th for team owner Roger Penske.
Marco, meanwhile, was battling the legendary "Andretti curse" at a track that has generally produced more maelstrom than milk-drinking for his family.
Unless you're Rick Mears, Al Unser or A.J. Foyt, you can't assess whether a fourth win is better than a first. Andretti, the 27-year-old son of his team owner Michael and grandson of auto racing legend Mario, is still chasing that elusive first one.
Maybe that's why Marco wasn't especially chatty after his fifth near miss in the race that matters the most to him and his family. Andretti has finished fourth or better in five of his nine Indianapolis starts.
But never first.
"We were close, but we never really dominated," Andretti said through a team spokesperson. "Every time we got to the front, we got shuffled back.
"I think we did what we could, but congrats to Ryan [teammate and race winner Hunter-Reay]."
Andretti basically finished third on a day when he had a third-place car. He got the maximum out of his Dallara-Honda package, but on this beautiful sunny day, it wasn't quite fast enough to beat Hunter-Reay and Castroneves.
"Marco gave it a heck of a shot," said Michael Andretti. "Unfortunately his car just wasn't quick enough there in the end. He drove a really good race, as it seems he always does here. He's one of the best drivers I've ever seen around this place."
Marco certainly gave it his all despite appearing to have too much downforce built into his car to allow it to compete for the win. He raced wheel-to-to wheel with Castroneves and Hunter-Reay, having several close calls.
"I think if it wasn't for the Indy 500, I would be pretty mad at Ryan," Marco Andretti said. "But it is for the Indy 500. He's up there and I'm not, so what are you going to say? I think this is as competitive as IndyCar has ever been, I don't care what anybody has to say."
Michael Andretti was lucky in the sense that he had two of the top three cars competing for the win. With Carlos Munoz and Kurt Busch also in the mix (they ultimately finished fourth and sixth, respectively) Andretti was looking good as long as Castroneves didn't prevail.
But Michael admitted that he felt conflicting emotions in the closing laps when he realized his son was probably going to fall agonizingly short yet again.
"I'm secretly watching [Marco], saying, 'C'mon, get up there! If you can pass him, do it!'" Michael said. "But I saw his car didn't have the speed. I think they were both really good, but I think [Hunter-Reay] was a little more trimmed, and had a little more speed. I knew at that point if we were going to win it, it would most likely be with Ryan.
"As a dad, you want him to be up here -- I can't lie," Michael Andretti added. "It would have been so special. It's special having Ryan here. When it's your kid, it's a different thing. It's a weird feeling because I really was disappointed for him. I know you only get that many shots.
"He had a car that was close, just not close enough. Yet I'm so happy and proud of the rest of the team. So it's a weird feeling. As a dad, disappointment. As a team owner, couldn't be happier. You have to try to balance those things."
Michael Andretti's third Indy 500 win as a team owner denied Roger Penske a record-extending 16th. But more importantly, Castroneves missed out on a prime shot at his own fourth win, the most important number in Indy lore.
Five years have now passed since his last triumph in 2009, and approaching 40 years of age, the ever-enthusiastic Brazilian surely won't have many more opportunities there for the taking.
Castroneves and Hunter-Reay raced hard but clean in the final laps when the race resumed after a brief red flag for track clean-up. Hunter-Reay darted almost into the grass approaching Turn 3 on Lap 198 to pass his rival from Team Penske; after ceding the lead to the Brazilian, the two racers crossed the line to take the white flag side-by-side before Hunter-Reay completed the race-winning pass with an outside move into Turn 1.
"I thought I didn't leave any room, but he found it," Castroneves said. "We're trying to do stuff that normally over 220 miles an hour you don't do it. When you have two experienced drivers battling that, it was a great show. I thought it was awesome.
"I had a great time," Helio continued. "I did everything I could to stop Hunter-Reay. I mean, at the end of the day there is stupid, and then there's bravery. I think we were right there on the edge, both of us, really trying.
"I'm glad we both came out in a good way. I'm just sad it did not come out the way I wanted."
Castroneves was particularly disappointed not to emulate Team Penske legend Mears, who scored two of his four Indianapolis race wins sporting a bright yellow Pennzoil paint scheme that the team memorably recreated on Helio's car this year.
With double points on offer at the Verizon IndyCar Series' three 500-mile races this year, the result moved Castroneves up to third place in the standings.
"Taking the positive out of this, it was a great race," Helio remarked. "I think the fans had a good time. We had a good day in the points. It certainly doesn't take away from the performance that we had.
"It's a shame, I wanted to give this to Roger so bad," Castroneves added. "It was a great fight. I'll tell you what, it was great TV.
"It's good when second sucks."