The Australian was one of the riders to come down in a high-speed crash shortly after the start of the stage, and his abandonment from the Vuelta was confirmed shortly afterwards on race radio.
Vine posted on social media after the stage, thanking his supporters for messages and giving an update on his condition.
“15 stitches, 10cm wound and it's GAME OVER,” posted Vine. "It was fun whilst it lasted.
“Thanks for all the messages. I'll be heading back home tomorrow, thanks to the team for sorting me out so quickly, sorry for not bringing the Pokadots (sic) home.
“Gutted is an understatement.”
Vine looked set to win the King of the Mountains competition thanks to his brace of victories in the opening week and his targeting of points in the days since. The 26-year-old had almost double the points haul of second-placed Richard Carapaz (INEOS Grenadiers) before the start of Stage 18 with 59 points to 30.
With only a few stages remaining, Stage 20 was shaping as the crucial stage for Vine to defend his KOM lead, but instead the final winner in Madrid will be someone else.
Carlos Rodríguez (INEOS Grenadiers) came down in the same crash as Vine, sustaining cuts to his left side and back, but he remained in the race after receiving treatment from the medical car.
Rodriguez looked the worse for wear throughout the stage and conceded time on the final climb, losing 1’19" to stage winner and race leader Remco Evenepoel (Quick-Step Alpha Vinyl) and slipping down to fifth overall at 6’49".
La Vuelta continues tonight with Stage 19 LIVE on SBS and SBS On Demand from 10:50pm (AEST).