The Giro was raced on a unique path through Italy, taking the peloton to some historic cities and towns in Italian cycling.

Though the route lacked any well-known, storied climbs, the many intermediate and mountain stages in the second and third weeks of the race proved deceptively difficult.

This protest was nominally about the overall safety conditions of the stage, and was sparked by life-threatening injuries sustained by Pedro Horrillo the day before.

In the protest, riders declined to contest the stage except for a final sprint finish, a decision that proved controversial with race organizers and fans.

Subsequent to the Giro, both he and third-place finisher Franco Pellizotti became embroiled in doping scandals, were given bans, and had their results stripped.

[13] Though his appearance was put in doubt after he crashed out of stage 1 of the Vuelta a Castilla y León and broke his collarbone, Armstrong announced on 16 April that he would start the Giro despite undergoing surgery for his injury.

[12][16] Many riders were named as contenders, including Ivan Basso, Levi Leipheimer, Armstrong, Damiano Cunego, Carlos Sastre, Gilberto Simoni, Danilo Di Luca, Marzio Bruseghin, and Denis Menchov.

[3] Pre-race analysis noted that Armstrong, when on his best form, would be a rider very likely to gain from having such a long race against the clock included in the Giro.

Race organizers were forced to alter this stage to cover only the Italian side of the Alps rather than also visit France, as there were concerns over radio communication in the area, and the roads stood the risk of landslides.

Race director Angelo Zomegnan responded to the criticism by saying, "I won't follow the philosophy that the selection of climbs has to be determined by their names.

[35] Cavendish was defeated in a sprint finish the following day by Italian Alessandro Petacchi, who was riding for the LPR Brakes–Farnese Vini team.

[45] Menchov was fifth after Alpe di Siusi, but rose to second before stage 12, the very long and hilly individual time trial in Cinque Terre.

Di Luca was nearly two minutes slower than him, finished sixth on the stage, and fell to second overall, with Menchov assuming the race lead.

[46] Di Luca tried repeatedly to shed Menchov during the remaining mountain stages to make up the time difference, which was never more than a minute.

The youth classification was won by Kevin Seeldraeyers, who remained consistent after Thomas Lövkvist lost nearly 25 minutes on stage 16.

[52] After spending five weeks in hospitals in both Italy and his native Spain, Horrillo eventually recovered,[53] though the day on the Culmine di San Pietro was his last as a professional cyclist, as he retired before the 2010 season began.

[54] The protest at first only involved the criterium being neutralized – that is, the race director agreed that each rider would receive the same finishing time as the stage winner regardless of when they actually crossed the line.

After four laps, they stopped altogether as race leader Di Luca addressed the unhappy crowd to explain their actions.

[57] Although the protest was referred to by some as "unanimous,"[56] cyclists such as Filippo Pozzato, who was himself bearing injuries sustained in a crash that would later force him to leave the race, said the riders had been too hasty in their decision, and that it should have been made conclusively before the stage began.

[58] Armstrong apologized to the fans for the effect the protest had on what was supposed to be a grand spectacle,[59] but also contended that it was the correct decision for the peloton to make.

Six different riders won multiple stages – Cavendish, Petacchi, Menchov, Di Luca,[44][61] Carlos Sastre,[47][62] and Michele Scarponi.

[67] About two months after the event concluded, on 22 July, it was announced that second place overall finisher and points classification winner Di Luca had given two positive tests for continuous erythropoietin receptor activator (CERA, an erythropoietin derivative) on 20 and 28 May, before the Cinque Terre time trial and the Mount Vesuvius stage in the race's final week.

[74] In October 2010, Di Luca was reinstated to active status by CONI, due to his cooperation with several ongoing doping investigations, though his results were indeed stricken from the record.

[76] Five days before the start of the 2010 Giro d'Italia, 2009 podium finisher Pellizotti was identified as a rider of interest to the UCI's biological passport program due to irregular blood values.

[80] The hearing was held in March, and Pellizotti asked for a quick resolution, with plans to return with Movistar Team in the 2011 Tirreno–Adriatico if he were cleared.

The court reached its decision after five days, upholding the UCI's appeal, handing Pellizotti a two-year ban, and stripping all his results from this Giro and the 2009 Tour de France.

[67] Other awards included the Combativity classification, which was a compilation of points gained for position on crossing intermediate sprints, mountain passes and stage finishes.