Australian contender Richie Porte is level with Britain's Chris Froome in the Tour de France, but both trail 67 seconds behind stage two winner and world champion Peter Sagan.
Porte suffered a flat tyre but managed to catch the peloton and finish the stage in 18th.
The BMC Racing rider moved up four places to 79th in general classification, but he lost another 16 seconds while his wheel was changed.
The Australian, who lost 51 seconds after being held up by other riders untangling themselves in stage one, is now 67 seconds behind Sagan.
The Slovakian was thrown out after the fourth stage 12 months ago for sending Mark Cavendish crashing in a chaotic sprint.
But he won it clean this time by beating Italy's Sonny Colbrelli and France's Arnaud Demare, in second and third places, respectively.
"It's a perfect day, I was a bit scared because Sonny was coming back strong," Sagan said.
"It's a very good start. I'm really back."
British defending champion Chris Froome also finished 182.5km ride from Mouilleron-Saint-Germain calmly on Sunday, after crashing himself the previous day, to remain level with Porte.
Froome is hoping to become the first rider since Marco Pantani in 1998 to achieve a Giro d'Italia-Tour double.
Other title rivals Vincenzo Nibali, Tom Dumoulin and Romain Bardet are 16 seconds behind Sagan, giving them an early advantage over Froome and Porte.
But stage two was a disaster for Australian sprinter Michael Matthews and stage one winner Fernando Gavira who were caught in a massive pile-up that split the bunch.
Matthews finished 148th on Sunday, after finishing seventh in stage one, while Gaviria ended up 28th.
Only about 15 riders were able to contest the final sprint.
Demare launched the sprint 250m from the line and Sagan jumped ahead of him with ease before holding off Colbrelli in the final metres.
Ethiopia's Tsgabu Grmay became the first rider to abandon the race on Sunday. His Trek-Segafredo team said he was suffering "intense abdominal pain."
Astana climber Luis Leon Sanchez later called it quits after he fell and bloodied his left arm.
The Tour remains in western France for stage three on Monday with a 35.5km team time trial that starts and finishes in Cholet.
Porte's BMC Racing team and Froome's Team Sky will both be looking to do well on the team time trial event on Monday.