In 2006, he was involved in an incident with Pedro Martínez. Martinez hit him with a pitch twice, and after the second time Guillén charged the mound, only to be held back by Paul Lo Duca and umpire Ted Barrett. Guillén appeared in only 69 games and hit only .216 with 9 homers and 40 RBI. On July 25, 2006, he was diagnosed with a tear of the ulnar collateral ligament in his right elbow, which would require ligament replacement surgery.