‘Hesjedal was a little stronger than me’ - Rodriguez
Going into the final individual time trial, the Spaniard had a 31-second lead over the more skillful sprinter Hesjedal, but trailed him 47 seconds on the streets of Milan.
It secured Hesjedal the top spot in the general classification and made him the first Canadian Giro winner, while Rodriguez and his Katyusha team were denied their maiden Grand Tour triumph.
"Every one of us did everything we could but Hesjedal was a little stronger than me," Rodriguez said on the Katyusha website.
"The gap between us was minimal, but it's pointless to talk now about where I could have won [or] where I could have lost this race, if I could have changed something or not," he said before adding: "That's cycling, every day is important here, every moment."
Rodriguez sweetened the pill a little by beating Britain's Mark Cavendish to win the red jersey in the points classification.
The 33-year-old joined Katyusha in 2010 and claimed one stage at the Tour de France that year. In his earlier years, he has grabbed the 2007 Spanish road race title and won the mountains classification at the 2005 Vuelta a Espana.