Bob Holly then underwent several surgeries to repair nagging injuries. He was hospitalized after a staph infection developed in a right arm wound. The infection was possibly career-threatening, as doctors were worried at one point that the arm may have to be amputated. The subsequent treatments were a success, however, and Holly made his in-ring WWE return at a RAW/SmackDown! supershow tapings on July 31, 2006 in a dark match, defeating Simon Dean.
Holly made a surprise appearance at WWE's Extreme Championship Wrestling house show event on August 21, 2006 in Allentown, Pennsylvania, defeating Balls Mahoney. Holly made his ECW television debut the next night, August 22, appearing in a promo with Paul Heyman, and later attacking Rob Van Dam and Danny Doring during a match. Holly, as a heel, soon joined with Heyman and his other associates to feud with RVD and others.
On September 26, 2006, Holly received 24 stitches from WWE Doctor Louis Rios in his back after suffering a severe laceration there during an Extreme Rules match against Rob Van Dam when he landed on the metal railing of a table he was suplexing Van Dam out of the ring and through during an ECW show in Tulsa, Oklahoma. Holly attained the injury early in the match but continued to wrestle for at least another 10 minutes with blood running down his back, despite his recent infections. After the match, as he was being helped out of the ring, he received a standing ovation from fans. The legitimate incident caused fans to cheer Holly in the following weeks, leading to a face turn and a feud with Paul Heyman's other enforcer Test. His second to latest run as a face was short lived as he eventually turned on Rob Van Dam when they were partners in a tag match.
When Sabu was found (kayfabe) unconscious in the back before the Extreme Elimination Chamber at December to Dismember, he was chosen as his replacement. Holly entered with Rob Van Dam as the first of two combatants. He was the second to be eliminated; he was eliminated by Test by a Running big boot.
Subsequently, he entered into a feud with CM Punk where by Holly, now a tweener, showed his endurance by surviving Punk's Anaconda Vice. Holly then gave Punk his first loss in ECW, Punk had been undefeated for half a year. After Test replaced Holly in a match against ECW World Champion Bobby Lashley, Holly vowed he would become champion whether he faced Test or Lashley. Holly then was one of ECW superstars entered in the Royal Rumble 2007, but was eliminated by The Great Khali. Holly soon became the #1 contender for Lashley's ECW Championship and faced off against Lashley, albeit unsuccessfully.
On April 3, 2007, Holly lost to Snitsky. After the match, Snitsky wedged Holly's arm between the steel steps and repeatedly hit the steps with a steel chair, resulting in a kayfabe broken arm. Hardcore Holly had surgery on April 16 because of a staph infection and missed around 5 months.
