Hamilton made a select group of four over the final climb of the stage, then in the finale when George Bennett (Jumbo-Visma) and Gianluca Brambilla (Trek-Segafredo) were messing around at the rear of the group, it was Hamilton that launched the decisive move.
Hamilton then had to re-catch Vendrama after the Italian rider counter-attacked and then played it cool in the lead-up to the sprint.
"Coming into the final with the four of us fighting for the win was pretty cool," said Hamilton. "I haven’t had so many chances for myself to go for a stage result so I’m really thankful to the team that I got the chance. Of course, I would have loved to win but second in a Grand Tour, yeah, I can say I’ve been there, you know. There’s not much else I could have done and I’m really happy with the day.”
Hamilton was beaten quite comfortably in the sprint, but had few regrets after the finish.
"Obviously, I really wanted to take the win but I know I gave it my all," said Hamilton. "Maybe I could have done the timing a bit different but in the end the strongest guy won."
The stage started out hard and fast, with seemingly every team trying to get representation in the early move. The longest stage to date in the Giro d'Italia with the most metres of vertical ascent was always going to be a difficult task for teams to chase and so it proved, with the break getting out to a maximum lead of 12 and a half minutes.
"It was a pretty hard day and I think everyone was expecting it to be a break,” said Hamilton. “It was the longest stage and it had the most altitude metres we’ve had at the Giro so far.
"We thought it would be a good opportunity to go for the breakaway. Nico Roche and I were given the green light to do that and after a massive fight I made it in. From then on it was about being as efficient as you could, not laying your cards out too early."
The Giro d'Italia continues tonight with Stage 13, a pizza-flat 198 kilometre stage from Ravenna to Verona. You can watch the race from 2015 AEST on SBS OnDemand, with SBS VICELAND coverage starting at 2120.