In 2013, Jeannie began developing a pilot with her husband titled The Jim Gaffigan Show. After working with NBC and CBS, the show landed at TV Land where Jeannie co-wrote and executive produced all 22 episodes with Jim. She directed the finale episode of Season 2. In August 2016, Jim and Jeannie decided not to continue with Season 3 of the show so they could spend more time with their family.

In July 2015, the Gaffigans appeared on the NPR program Ask Me Another, where Jeannie played a version of the Newlywed Game; she got all the answers right.

In May 2016, the Gaffigans delivered the commencement address at the Catholic University of America.

In April 2017, Jeannie was diagnosed with a benign brain tumor known as papilloma of the choroid plexus. She had endured several months of symptoms such as headaches and dizziness, thinking they were simply caused by everyday stress, but went to the Doctor when she began to lose her hearing. The tumor was the size of an apple and doctors believed it had been growing for more than a year. On April 18, Dr. Joshua B. Bederson successfully removed the tumor in a nine-hour surgery at the Mount Sinai Health System in New York City.