Since turning professional in 2006, Santiago Giraldo has competed in lower events at Buenos Aires, Bogotá and Asunción. He reached the final at Bogotá in October 2007 but he lost out in straight sets. Giraldo reached his first Grand Slam main draw at the 2007 French Open, where he lost to Novak Djoković.
At the 2010 Internazionali BNL d'Italia in Rome, a Masters 1000 event, he produced a heavy ground game to crush down 12th seed Juan Carlos Ferrero 6–0, 6–3 in the first round, followed by a 6–3, 6–2 win over Michaël Llodra in the second round. However his run was ended at the hands of World No. 10 and 7th seed Jo-Wilfried Tsonga 3–6, 4–6 in the third round.
In May 2014, Giraldo surprised Jo-Wilfried Tsonga in the second round of the 2014 Mutua Madrid Open beating the 11th seeded Frenchman in straight sets 6-4, 6-3. Then he achieved his first win against a top 10, after defeating the World No. 8 and two-time Grand Slam champion Andy Murray in straight sets 6-3, 6-2. He advanced to the quarterfinals but lost to Roberto Bautista-Agut.
Giraldo is known for consistently taking huge cuts at the ball, flattening out every forehand and backhand possible when he is able to get a firm grip on the ball. However, such a style of play evidently generates a higher chance of unforced errors. Giraldo is good at returning serves.
Won tournament; or reached Final; Semifinal; Quarter-final; Round 4, 3, 2, 1; competed at a Round Robin stage; lost in Qualification Round; absent from tournament event; played in a Davis Cup Zonal Group (with its number indication) or Play-off; won a bronze, silver (F or S) or gold medal at the Olympics; a downgraded Masters Series/1000 tournament (Not a Masters Series); or a tournament that was Not Held in a given year.
To avoid confusion and double counting, these charts are updated either at the conclusion of a tournament, or when the player's participation in the tournament has ended.