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After battling with Marc Marquez, Pedro Acosta and Jorge Martin early on for the race lead, factory Ducati rider Bagnaia slipped to fifth place at the chequered flag, finishing over seven seconds behind race winner Maverick Vinales.
Not only did Bagnaia lack the pace to stay with Aprilia's Vinales and second-placed Acosta on the KTM in the second half of the 20-lap contest, he also could not put up a fight to the Ducati GP24s of team-mate Enea Bastianini and Pramac rider Martin, as he lost touch with the lead pack.
The Italian ran with a soft rear tyre at the Circuit of Americas, a choice that helped Bastianini to grab third position on lap 18, having successfully tested the longevity of the compound in the warm-up earlier on Sunday.
But a return of the tyre vibration problem that plagued him in the Qatar sprint and impacted his Portugal weekend meant he had no option but to conserve his position and salvage as many points as possible in Austin.
"My race started well, I was feeling good. I was thinking after lap six that I was able to fight for a win or a podium," he said.
"But I started to have a lot of chattering, a lot of vibrations on the left side and it was very difficult to manage everything.
"I completely destroyed the tyre on the right side. So, it was also difficult to do corners on the right side.
"So, I raced in defence after seven laps, six laps, and it was very difficult. I tried to manage everything but like this, for sure we have to understand the situation and solve the problems because right now it's very difficult.
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"The situation is very similar to 2022, that in the start of the season I had to race in defence. All my trust is in my team that we will solve the problem. We will be battling for the top again."
The US round was arguably Ducati's least competitive weekend of 2024, as Vinales recovered from 11th on the grid to take a stunning victory and Tech3's Acosta finished second to leave Ducati as the third-best marque.
Saturday's sprint was also rough for the Italian manufacturer, with Bastianini and Bagnaia only managing sixth and eighth - although Martin did grab third place on the Pramac.
Asked if he was worried about the chattering issue, given how difficult it is to solve for engineers, Bagnaia said: "It's strange because Enea didn't have any chattering this weekend, but he was really in trouble all weekend.
"I was feeling good, Martin was fast, but today we struggled. So, it's difficult to understand with three bikes, because Franky [Morbidelli] is still learning so it's difficult to put him on the same package.
"Enea was struggling with the brakes, struggling to let the bike turn. But today was super fast and without problems [I] was able to fight for the win. I was able to fight for the win for just six laps, and after that I started to struggle."
Reigning champion Bagnaia sits fifth in the standings after the opening three rounds of the season, already 30 points off championship leader Martin. However, the picture in the riders' table is skewed by the 27-year-old's DNF in Portugal, caused following a collision with Marquez.