These two clubs met once earlier this season, way back on Nov. 2, when the Flames had a six-game winning streak snapped in a 3-2 OT loss, Matt Duchene scoring the game-winner 1:37 into extra time.
Tuesday's game was billed as a potential playoff preview, as the two teams would be playing each other if the postseason started today.
And it didn't disappoint.
Dan Vladar made his 15th start of the season, stopping Filip Forsberg and Matt Duchene in the shootout before Mikael Granlund beat him for the winner. Vladar finished with 25 saves.
At the other end of the ice, Juuse Saros denied Johnny Gaudreau, Matthew Tkachuk and Tyler Toffoli in the shootout, and made 19 saves on the night.
Despite the loss, the Flames - playing their fifth game in eight days and second in the last 48 hours - picked up a big point in their continuing quest to secure the Pacific Division crown.
Meanwhile, Mangiapane's two goals were his 33rd and 34th of this breakout campaign for the young forward. He now has four goals in his last five games.
Gaudreau picked up his 108th point on the goal, while Tkachuk also got an assist, his 99th point of the year.
He eclipsed the career-high 98 points his dad, Keith, recorded with the Winnipeg Jets in 1995-96.
Keith and Tkachuk's mom, Chantal, were at the game after attending the Flames 5-2 win in Chicago Monday night.
Forsberg beat Vladar but his shot clanged off the far post with 8:48 left to go in the first period on the best early chance of the night.
On the ensuing rush, Elias Lindholm fed it to Rasmus Andersson who snuck up into centre and he passed to Gaudreau, who slipped around Alexandre Carrier with a nifty move and tried to slid a backhand five-hole but was slashed by Forsberg.
The Flames generated some pressure on the man-up but had a hard time getting pucks on Saros, recording just one shot.
Vladar made a 10-bell stop on Luke Kunin after a puck ended up out front in the blue paint and the Preds forward was in perfect position to hit it home.
It was a solid period for the netminder, who faced nine shots, while the Flames recorded five.
Calgary came out flying in the second, hemming Nashville in and applying pressure, but went a man down after Tkachuk was tagged for roughing on Nick Cousins in front of the Predators net.
The Flames fifth-ranked PK - which came into the game at 84.1% - got the job done and killed it off.
Not long after, former Predator Calle Jarnkrok had his turn losing a battle with the iron, clanging one off the post.
The Flames went back on the PK at 6:28 when Nikita Zadorov was whistled for a hook, Calgary getting a nice chance when Mangiapane and Toffoli had a 2-on-1 shorthanded break, Mangiapane keeping it, then toe dragging around a sliding defender but his shot deflecting high over the net.
The Preds then cashed in, Forsberg one-timing a pass from Ryan Johansen off the post and past Vladar at 7:23.
They made it 2-0 at 12:09 when Duchene scored his 40th of the season.
Mangiapane's first goal came on the powerplay at 15:13 after Gaudreau stepped into a shot and the rebound went off Tkachuk and dribbled back across the crease where No. 88 smacked it in.