Despite a franchise-record 57 shots on goal Tuesday against Nashville, the Sharks allowed the visiting Predators to rally for a 4-3 overtime victory.
San Jose (13-3-1), which opened the season 9-0-0 at home, suffered consecutive losses for the first time this season, but maintained the NHL's best record.
Devin Setoguchi tied a franchise record with 10 shots on goal, scoring twice and assisting on another goal. His second score put San Jose ahead 3-2 with less than 14 minutes left, but the Predators got the equalizer at the 13:33 mark, and Villie Koistinen netted the winner 2:28 into overtime.
Brian Boucher, filling in for an injured Evgeni Nabokov, lost his second straight and allowed a season-high four goals on 29 shots. Boucher has allowed seven goals in his last two starts after going 3-0-0 with two shutouts in his first three games.
Boucher will start again on Thursday as Nabokov did not practice Wednesday and remains day-to-day with a leg injury.
"Sometimes you get in a zone, and play is going to be easier from time to time," said Boucher, who is 0-2-0 with a 2.51 goals-against average lifetime against the Flames. "We're pretty upset to get up against a team like that and not get two points. It's very disappointing."
Calgary (9-7-1) is coming off Tuesday's 4-3 victory over Toronto, just its second win in six games.
"That last goal was a fluke. The good news is we had that cushion," Flames coach Mike Keenan said. "I've never seen a goal go in like that - ever."
Starting all but one game this season, Kiprusoff has allowed 22 goals in his past five starts. He is 9-6-1 with a 3.31 GAA in 2008-09 after posting a 2.69 mark in 76 games last season.
Kiprusoff, who spent his first three seasons with San Jose, has one win in his last six games against his former team, including last season's playoff matchup. In Game 3 of that series, Kiprusoff gave up three goals in the first 3:33 and was pulled before Calgary eventually rallied for a 4-3 victory.
"It's just a matter of confidence," Boyd said. "When you're playing with confidence, you just go with the flow and good things happen. Tonight, I was lucky enough to play with Jarome and it was a good night."
After going five games without a goal, Iginla has scored four times in the last four games and leads the team with 21 points. He has recorded a point in 13 of his last 17 games in San Jose and has scored a goal in five of his past seven contests at HP Pavilion.
The Sharks won last season's quarterfinals matchup in seven games on the strength of three straight home victories. San Jose is 2-0-2 in its last four regular-season home games against Calgary.