Another victory this weekend would not only be the 500th grand prix win for Yamaha, but end reigning MotoGP champion Marc Marquez's stranglehold on the COTA event.
Since the Texan circuit joined the calendar in 2013, Marquez has won every MotoGP race from pole position. But the Honda rider is already on the back foot after falling from the lead in Argentina and many feel that if Vinales can beat Marquez in Austin, he can beat him anywhere.
"The next round is Austin and I'm happy because it's where I won my first race in Moto2 and did one of my best races with Suzuki. I've always been very strong here," warned Vinales, fourth in the 2016 event.
"I think it is an excellent circuit for my riding style, I love the up and down track, with lots of elevation, so I'm so excited to see how my M1 will work here and how I'm going to feel riding the Yamaha. I'm confident and I know that I can do another good race weekend."
While a Yamaha has never seriously challenged for COTA victory in the past, team director Massimo Meregalli is convinced that can change at the hands of Vinales or team-mate Valentino Rossi this weekend.
"The track lay-out is quite interesting and, though previously it didn't play to our advantage, we will start this race weekend in full-attack mode," he said. "We will use the first free practice sessions to understand how to make this race another great one for Yamaha, as we strive for the 500th victory.
"Our riders are both in great form and both enjoy the Grand Prix of The Americas. We are looking to get some strong results again and can't wait to get started!"
Vinales starts round three with a 14-point lead over Rossi in the world championship standings.