The 3-year-old colt was scratched hours before the Run for the Roses after trainer Jeff Mullins discovered a hot spot on the horse's left front ankle.
"We could tell he was not 100 percent," Mullins said.
An X-ray did not find any damage, but with a wet track expected for the Derby, Mullins and owner David Lanzman didn't want to take any chances.
"When the word came out that running could hurt the horse, I looked at both doctors and said 'Then there is no debate,'" Lanzman said. "We'll fight another day."
Larry Bramlage, the on-call veterinarian at Churchill Downs, said the horse didn't look injured while jogging for doctors.
"Unfortunately, this close to the Derby, there's not a way to gauge how bad that is," he said.
I Want Revenge and 19-year-old Joe Talamo were to start from post No. 13. The duo established themselves as one of the Derby favorites after a last-to-first dash in the Wood Memorial last month.
Mullins said he doesn't expect the injury to be career-threatening but will give his star some time off before deciding what to do next.
"We're going to do the right thing by him," Mullins said. "The doctors said he'll come back 100 percent."