Simon is tied with Zack Greinke of Los Angeles and St. Louis' Adam Wainwright for the most wins in the NL with nine and has won three straight and five of his last six starts. Simon tossed eight innings of one-run ball in a 4-1 win over the Dodgers last Thursday, pushing his record to 9-3 with a 2.95 ERA.
The right-hander had allowed 11 runs in his previous three starts. Simon is 6-1 in seven road starts this season and 2-3 with a 2.57 ERA in 15 career games (1 start) against the Pirates.
Cincinnati is 10-3 when Simon takes the mound this season.
The Reds have won five of six and seven of their last 10 games, and opened this Steel City series with Tuesday's 6-5 win. Todd Frazier led off the top of the ninth with a home run off Pirates reliever Jason Grilli and finished with two hits and a pair of runs scored.
"He threw me two straight sliders and I was hoping to get a fastball there and I did," Frazier said of his at-bat against Grilli.
Joey Votto drove in three runs and Billy Hamilton ended 3-for-4 with two runs scored, as the Reds improved to 3-1 on a six-game trek. Johnny Cueto did not figure into the decision and was reached for two runs in six innings. Logan Ondrusek got the win in relief and Aroldis Chapman struck out two in the ninth to record his 12th save.
Pittsburgh hopes to even this set with Cincinnati and failed to come out on top in this see-saw affair on Tuesday. Grilli was dealt the loss and Brandon Cumpton pitched well in the start, allowing three runs in six innings with four strikeouts and one walk.
"We missed a couple of opportunities," said Pirates manager Clint Hurdle. "We did what you need to do to put yourself in position to score."
Josh Harrison collected four hits and two RBI, Russell Martin drove in two runs and Ike Davis ended 2-for-4 with an RBI and a run scored for the Pirates, who are still 16-10 in the last 26 games. Andrew McCutchen finished 1-for-4 with a run scored and extended his hit streak to 12 games.
Pirates young prospect Gregory Polanco has hit safely in his first seven major league games. The last Pirates' player to do so was Roberto Clemente in 1955.
"I know about that," Polanco said on the club's website, "but I don't think about it at all. I can't. All I can do is keep going out there and continue playing the way I have."
Pittsburgh has gone 12-7 in the last 19 games played at PNC Park. The Pirates have also gone 5-1-1 in their last seven series there and are 7-3-1 in series played overall at home.
Edinson Volquez aims for another superb start when he takes the mound for the Pirates Wednesday. Volquez threw seven shutout innings in a 4-0 win over the Chicago Cubs last Thursday, improving to 4-5 with a 3.89 ERA. He has won three of his last four decisions.
Volquez, a former Red, has made four career starts against Cincinnati and the right-hander owns a 1-1 mark to go along with a 3.55 ERA.
Pittsburgh has lost six of its eight matchups with the Reds this season.