Clemens made his 2007 return on June 9, defeating the Pittsburgh Pirates by pitching six innings with seven strikeouts and three runs allowed. On June 21, with a single in the 5th inning against the Colorado Rockies, Clemens became the oldest New York Yankee to record a hit (44 years, 321 days). On June 24, Clemens pitched an inning in relief against the San Francisco Giants. It had been 22 years and 341 days since his previous regular-season relief appearance, the longest such gap in major league history. On July 2, Clemens collected his 350th win against the Minnesota Twins at Yankee Stadium, giving up just two hits and one run over eight innings. Clemens is one of only three pitchers to pitch his entire career in the live-ball era and reach 350 wins. The other two are Warren Spahn (whose catcher for his 350th win was Joe Torre, Clemens's manager for his 350th), and Greg Maddux, who earned his 350th win in 2008. His final regular season appearance was a start against the Red Sox at Fenway Park, in which he allowed 2 hits and 1 unearned run in 6 innings, and received a no-decision. Clemens finished the 2007 regular season with a record of 6–6 and a 4.18 ERA.
On January 6, 2008, Clemens went on 60 Minutes to address the allegations. He told Mike Wallace that his longevity in baseball was due to "hard work" rather than illegal substances and denied all of McNamee's assertions that he injected Clemens with steroids, saying it "never happened". On January 7, Clemens filed a defamation lawsuit against McNamee, claiming that the former trainer lied after being threatened with prosecution. McNamee's attorneys argued that he was compelled to cooperate by federal officials and so his statements were protected. A federal judge agreed, throwing out all claims related to McNamee's statements to investigators on February 13, 2009 but allowing the case to proceed on statements McNamee made about Clemens to Pettitte.
On February 13, 2008, Clemens appeared before a Congressional committee, along with Brian McNamee and swore under oath that he did not take steroids, that he did not discuss HGH with McNamee, that he did not attend a party at José Canseco's where steroids were the topic of conversation, that he was only injected with B-12 and lidocaine and that he never told Pettitte he had taken HGH. This last point was in contradiction to testimony Pettitte had given under oath on February 4, 2008, wherein Pettitte said he repeated to McNamee a conversation Pettitte had with Clemens. During this conversation, Pettitte said Clemens had told him that McNamee had injected Clemens with human growth hormone. Pettitte said McNamee reacted angrily, saying that Clemens "shouldn't have done that."
In April 2008, the New York Daily News reported on a possible long-term relationship between Clemens and country music singer Mindy McCready that began when she was 15-years-old. Clemens's attorney Rusty Hardin denied the affair and also stated that Clemens would be bringing a defamation suit regarding this allegation. Clemens's attorney admitted that a relationship existed but described McCready as a "close family friend". He also stated that McCready had traveled on Clemens's personal jet and that Clemens's wife was aware of the relationship. However, when contacted by the Daily News, McCready said, "I cannot refute anything in the story."
On November 17, 2008, McCready spoke in more detail to Inside Edition about her affair with Clemens, saying their relationship lasted for more than a decade and that it ended when Clemens refused to leave his wife to marry her. However, she denied that she was 15 years old when it began, saying that they met when she was 16 and the affair only became sexual "several years later". In another soon-to-be-released sex tape by Vivid Entertainment she claimed that the first time she had sex with him was when she was 21. She also said that he often had erectile dysfunction. A few days after the Daily News broke the story about the McCready relationship, they reported on another Clemens extramarital relationship, this time with Paulette Dean Daly, the now ex-wife of pro golfer John Daly. Daly declined to elaborate on the nature of her relationship with the pitcher but did not deny that it was romantic and included financial support.
There have been reports of Clemens having at least three other affairs with women. On April 29, 2008, the New York Post reported that Clemens had relationships with two or more women. One, a former bartender in Manhattan, refused comment on the story while another, a woman from Tampa could not be located. On May 2 of the same year, the Daily News reported a stripper in Detroit called a local radio station and said she had an affair with Clemens. He also gave tickets to baseball games, jewelry, and trips, to women he was wooing.