During the critical smallpox outbreak, Pratt proves his skills and courage as a swift physician by helping Dr. Luka Kovač and Dr. Jing-Mei Chen save Dr. Romano's life.

The hospital is thrown into chaos during the evacuation gone awry, and he along with Dr. John Carter, Abby Lockhart, and Dr. Jing-Mei "Deb" Chen is forced to quarantine in the ER.

Pratt and medical student Michael Gallant were briefly held for questioning by the Chicago police after a robbery/homicide occurred at a diner across the street; Chen had said that she might have seen a black man fleeing the scene.

However, Romano never got to present these findings before the hospital director since he never showed up at the conference (unbeknownst to the others, he had been killed minutes earlier by a helicopter that crashed in the ambulance bay and crushed him).

Their interactions became infrequent due to Chen's family problems, but Pratt went over to her house during Season 11's Christmas Eve episode when he learned she quit.

However, he decided against applying for the position due to the extra workload, which was subsequently awarded to Dr. Archie Morris- who was goofy and awkward and had none of Pratt's natural leadership and communications skills.

But, following on in Season 12, Pratt was unable to forgive his father for their estrangement even though proof emerged that Charlie had been forced out of Greg's life by his mom, and ended any reconciliation efforts.

At the start of season 13, Pratt achieves his new title as attending, while Chaz moves in with him after Charlie abuses him and he joins Greg in cutting all ties to his rotten dad.

He also supports his brother's new job as an Emergency Medical Technician but clashes with Chaz's co-workers after they encourage him to drink near-fatal amounts of alcohol.

Surprisingly, Pastor Watkins of First Mission Baptist and his congregation showed up on Pratt's behalf and explained the entire story of his contribution.

After being overlooked for the position of Chief of the ER in favor of a new attending Dr. Skye Wexler, Pratt submitted his two-week notice of resignation stating that the administration of the County General did not respect him; however, he soon changed his mind after meeting former Physician Assistant Jeanie Boulet.

At the end of the Season 14 finale, "The Chicago Way," Pratt entered an ambulance, which was transporting a patient (portrayed by Steve Buscemi), who revealed himself to be a government informant in Witness Protection.

Among the ER staff who came to memoralize him at Ike's bar were Dr. Abby Lockhart, Dr. Archie Morris, Dr. Neela Rasgotra, Dr. Tony Gates, Sam Taggart, Simon Brenner, Chuny Marquez, Haleh Adams, Malik McGrath, Frank Martin, Paramedic Dumars, and his brother Chaz, who had become a new med student about halfway through Season 15.