"We came into the week looking for clarity on John's knee, hoping it would respond the way it has," team captain Jim Courier said at Thursday's draw ceremony. "He practiced hard every day. He's had no setbacks.
"From our eyes and our medical staff's eyes, we feel confident he's ready and set for 10 sets of tennis if he needs to play them this weekend."
Isner injured his knee a month ago at the Hopman Cup in Perth, Australia playing with Venus Williams. He withdrew in his opening match the following week at the APIA International Sydney and hasn't played competitively since.
He said he's ready to return to the courts.
"I had a very encouraging week of practice which is what I was looking for," the 6-foot-9 Isner said. "I didn't know how my knee was going to react when I really started to practice hard because it's been a while.
"My knee hasn't been bothering me. I feel like I'm ready to go."
Isner's presence in the lineup is key to the Americans' hopes of beating Brazil and advancing to the quarterfinals in April against the winner of the Serbia-Belgium. Isner is the 13th-ranked player in the world, the best ranking of any of the four singles players competing in Friday's opening match.
He will meet Brazil's Thiago Alves, ranked No. 145 in the second singles match on Friday. The opening match pits the United States' Sam Querrey (No. 22) taking on Brazil's top player, Thomaz Bellucci (No. 33). It's the first meeting for the players in both matches.
The doubles competition takes place on Saturday with the world's No. 1 ranked team of Bob and Mike Bryan taking on the Brazilian pair of Marcelo Melo and Bruno Soares who have a 17 and 19 doubles ranking respectively.
Had Isner been ruled out, the U.S. likely would have turned to Ryan Harrison who last summer cracked the Top 50 rankings for the first time.
The match marks the fifth meeting between the U.S. and Brazil in Davis Cup with the Americans leading the overall series 3-1. The countries last met in Davis Cup play in 1997 in a first-round match in Ribeirao Preto, Brazil. Courier played singles for the U.S. team and won two matches to lead the American team to a 4-1 win.
This will be the first Davis Cup competition in an American city for either Isner or Querrey. Isner is 5-5 in Davis Cup singles play while Querrey is 1-5, with all matches held outside the U.S. on clay courts.
Isner, who lives in Tampa and played his college tennis at nearby Georgia, is looking forward to having the home crowd support behind him and his teammates.
"I've always flown over an ocean to go play Davis Cup. This tie I just got in my car and drove three hours," he said. "I do feel at home here. Hopefully I can get some USA chants, but Georgia chants also would be accepted on my part."
While the Bryan brothers have the world's No. 1 ranking and are coming off another Grand Slam doubles title at the Australian Open two weeks ago, the Brazilian pair of Melo and Soares hold a 2-1 edge on the U.S. pair. The four players met for a fourth time this past December when they played an exhibition match in Brazil. The Bryan brothers were victorious in three sets.
"This is a team that has beaten us before," Bob Bryan said. "We really respect them. But yeah, it's going to be a war.
"These guys are both top-20 players, both won tournaments this year, so they're playing well. We know what we have to do. We feel good. We have some momentum coming here from Australia. But that definitely doesn't mean it's going to be easy."