Rose returned to full contact practice in January 2013, and was cleared by doctor to play that March, but he did not appear in a game during the 2012–13 NBA season. Despite Rose's absence, the Bulls advanced to the Eastern Conference Semifinals, where they lost to the eventual champions, the Miami Heat.
Rose's much awaited return came on October 5, 2013, in a pre-season game against the Indiana Pacers. He had a slow start but scored his first point in the first quarter. He finished the game with 13 points in 20 minutes of play. On October 16, 2013, Rose returned to play in Chicago for the first time, scoring 22 points against the Detroit Pistons. "I think I'm way more explosive now. Like getting to the rim. I think I can take contact a little bit better. And as far as jumping-wise, I think I can jump even higher. They tested my vertical -- I increased it by 5 inches", Rose said after the win. During the pre-season, Rose averaged 20.7 points and 5 assists.
His first official game was in 107–95 loss against the defending champions Miami Heat on October 29. Rose was limited to 12 points, while having 4 assists in 34 minutes of play. He played his usual minutes, but was inefficient from the field, shooting 4–15. Two days later, he played his first official home game against the New York Knicks where he hit the game-winning floater in an 82–81 win. He had 18 points, 6 rebounds and 3 assists. On November 3, 2013, Rose scored 13 points and committed 8 turnovers in the loss against the Philadelphia 76ers. He struggled in his return, shooting 28.8% from the field and averaging 5.7 turnovers in his first three games.
On February 24, it was announced Rose required another round of surgery on his right knee and was ruled out indefinitely. An exam and subsequent MRI confirmed a medial meniscus tear of the right knee, the same injury he sustained on November 22, 2013 against the Portland Trail Blazers. On February 27, he was deemed a possibility of returning toward the end of the season after he underwent successful surgery and was ruled out for just four to six weeks.