The four-year-old took the lead heading around the Moonee Valley bend, but could not hold off fast-finishing duo Sir Dragonet and Armory, with the former bolting away to win by more than a length.
Russian Camelot jumped as a $3.50 favourite, one of three Irish-bred horses to fill the placings of the time-honoured Group One classic.
But O'Brien — along with champion jockey Damien Oliver — was pleased with the performance, and said the November 3 Melbourne Cup remained on the cards.
“Damien (Oliver) gave him a superb ride from that gate and he probably got left there a bit early too, he was a sitting shot for the two that went by him,” O'Brien said.
“He had to go forward on what was a pretty hot tempo, I think he's the only one that's held on from up front. You can't always win and you can only ask for 100 per cent effort from the horse.
“Albeit he hasn't won today, but that was his best performance, Damien was very proud of him, he's never put in more than he has done today. We're really proud of him.
“We've always thought we would go to the Melbourne Cup, provided we are happy, and he's run out of his skin again today, so we're happy. We'll see over the next 10 days, but at this stage you'll see him at Flemington on Tuesday week.”
Russian Camelot remains on the the fourth line of betting for the 3200 m Group One, at $11.
O'Brien celebrated victory earlier in the day, with Sovereign Award leading from start to finish in the Group Three Powerflo Solutions Stakes.
Ridden perfectly by in-form jockey Jamie Kah — who picked up four winners for the day — the five-year-old mare held off the chasing pack to win the $200,000 race, with another O'Brien horse Paradee finishing third.
Sovereign Award has now won her past three starts, including another Group Three at her previous start.
O'Brien denied Lindsay Park legend So Si Bon a Gold Star on Friday night, with Iconoclasm winning the race for a third straight year.
The Euroa stable's seven-year-old was sent out as a $2 favourite and looked the goods when hitting the front 150 m from home, before Iconoclasm fought back and grabbed a narrow win.
The win took the horse past $1 million in prizemoney.
