Spadea has ATP career singles wins over Roger Federer (1–2 record), Pete Sampras (1–4), Andre Agassi (2–4), Rafael Nadal (1–1), Andy Roddick (1–2), Pat Rafter, Richard Krajicek, Yevgeny Kafelnikov, Jim Courier, Michael Chang, Marat Safin, and Gustavo Kuerten.

He continued his journey back up the world rankings and was back in the top 20 by late 2004, although US Davis Cup captain, Patrick McEnroe, declined to pick Spadea as his second singles player for the 2004 Davis Cup final against Spain, opting instead for the lower ranked Mardy Fish.

In 2006, Spadea published his autobiographical book, Break Point: The Secret Diary of a Pro Tennis Player.

[5] Spadea criticized a number of tennis players including James Blake and Davis Cup captain Patrick McEnroe.

He called out McEnroe for picking Mardy Fish ahead of him for the 2004 Davis Cup final where the Americans lost to Spain.

Vince had an injury-stricken season in 2009, plagued by an overuse tendonitis arm issue, as well as a lower extremity staph infection.

He won only a handful of ATP-level singles matches before the start of the clay-court season, but reached the semifinals of the Carson Challenger.

The New York Times summarized his career by calling him "the epitome of a tennis journeyman" and then noted that "he has played in 15 US Opens and has never reached the quarterfinals.