The Bills are converting from a 4-3 defense under new head coach Chan Gailey and coordinator George Edwards. That will turn the AFC East into a unanimous 3-4 division.
The Bills ran a Tampa 2 defense under former head coach Dick Jauron and his interim replacement, Perry Fewell.
Ryan, considered one of the finest 3-4 masterminds, noted the transformation can be smooth.
"I guess that depends on 'Are you changing coverages or is it just the front you are changing?'" Ryan said Saturday at the NFL scouting combine in Lucas Oil Stadium. "There are several different versions of a 3-4. But it depends on your style.
"If the coverages are staying the same, it probably is not as big of a change as what you might think."
The problem for Buffalo, however, is that they're missing the centerpiece of a 3-4 defense: a monstrous nose tackle to stuff the run.
"That might be one of the toughest parts of a 3-4," Ryan said.
Ryan went on to explain why.
(Football jargon alert! "Two-gap responsibility" means a defensive lineman is responsible for either opening beside the offensive lineman in front of him. "A-gap" means the area on either side of the center, a location where defensive linemen frequently will get double-teamed by a center and a guard.)
"If you are playing a standard 3-4 defense, then you got a two-gap responsibility, which means you got to be able to play the front-side A-gap and the backside A-gap at the same time," Ryan said.
"You generally need a dominant individual there. And that is what you have like a Kris Jenkins. A Ted Washington many years ago in Buffalo was one of the best two-gappers I have ever seen.
"A guy has to be active, got to be able to stay on his feet, his technique on releasing off of blocks has got to be outstanding. If not, you are really going to struggle at that spot."
The Jets are the only AFC East team that didn't make a change at defensive coordinator.
The Miami Dolphins fired Paul Pasqualoni and snatched Mike Nolan away from the Denver Broncos. Although the New England Patriots' defense belongs to head coach Bill Belichick, coordinator Dean Pees stepped down in January.
Nolan was the Baltimore Ravens' defensive coordinator when Ryan was their defensive line coach. When Nolan left to become head coach of the San Francisco 49ers in 2005, Ryan was appointed defensive coordinator.
Ryan, never afraid to throw out a challenge, was deferential when asked about facing Nolan twice a year.
"He's outstanding," Ryan said. "He's one of the top coordinators in the league. I learned a ton working under Mike for several years. He's one of my favorite guys. That was a great hire.
"He's always had a well-coached team that really gets after it. I'm sure that's the way it'll be. It's going to be tough."