Pagano, 52, in September was diagnosed with acute promyelocytic leukemia and took an indefinite leave of absence from coaching. In early November, doctors said the cancer was in remission and last week Pagano was cleared to return to coaching duties.
"I'm ready to go," Pagano said Monday. "Dr. (Larry) Cripe told me, 'Be prudent, be smart how you attack this thing.' ... I still have a strict regimen to stick to. There's a plan for the next few years and the years after that. ... I feel great. My weight's back. My energy's back."
The Colts were 1-2 when Pagano left the team and have posted a 9-3 record with Bruce Arians as interim coach. Indianapolis (10-5) has qualified for the AFC playoffs.
Arians was with Pagano for Monday's news conference.
"I asked him if he would ... take over the reins and what a masterful, masterful job you did Bruce," Pagano said. "You carried the torch and all you went out and did was win ballgames, you got our 10th win yesterday and you got us into the playoffs and you did it with dignity and you did it with class."
Pagano is expected to be on the sidelines Sunday when the Colts play the Houston Texans at home in the final regular-season game.
It was an emotional return for Pagano, who singled out his wife.
"The happiest day of my life was July 1, 1989 -- that's when I got married to my wife, Tina," he said with tears in his eyes. "I want to thank you. She's a soldier, a warrior, my soul mate. You can't get through this without somebody as strong and as loving, and I thank you, Tina."