The testimony was a body blow to the prosecution in Clemens' Washington trial for allegedly lying to Congress about not taking steroids and the hormone, The New York Times reported.
Pettitte, 39, had testified Tuesday Clemens had told him in 1999 or 2000 he had used the human growth hormone. The hormone, or HGH, is banned by Major League Baseball and is designed to enhance performance.
But Wednesday, Pettitte was not so sure.
Defense lawyer Michael Attanasio asked him, "As you sit here today, you believe in your heart of hearts and your mind that you very well might have misunderstood Mr. Clemens. Sitting here now, you're 50-50 that you misunderstood him, is that fair?"
Pettitte answered, "I'd say that's fair," swiveling his seat away from Clemens, sitting about 25 feet away, the Times reported.
Clemens, who spent 23 years in baseball as a pitcher on various teams, was indicted in 2010 on six counts, including perjury and obstruction of Congress.
His first trial ended in a mistrial last year because of alleged prosecutorial misconduct.