Several of the children have rare genetic diseases including sickle cell anemia, giant axonal neuropathy and various other immunodeficiency diseases, according to the hospital spokeswoman.
Families stay at the NIH inn to participate in clinical research -- diving into the behavior and nature of living systems -- to try to reduce the burdens of illnesses and disabilities on children.
It is now the third year Trump has visited the inn on Feb. 14.
Trump wore red as she met with the children -- including some on bed rest -- and helped to craft special valentines.
One child that was hooked up to oxygen tanks and several IVs, raised a small thin arm to wave at the first lady.
She was greeted by Jennie Lucca, the inn’s CEO, director and vice chair, and approximately 15 patients -- almost all under the age of 10.
The first lady spent her time seated at the tables adorned with pink and red -- helping to decorate the cut-out sugar cookies with icing, as the children showed her their heart decorations made of paper maché.
She told the kids, "Stay strong, we will think of you and pray for you, you will be in my thoughts."
Just before leaving, Trump handed out her own red Valentine’s Day cards to all the children and addressed the staff.
"I’m so glad to be seeing the children feeling well ... thank you for all that you do and keeping strong," she told the staff and families. "This is a great place and have a great team to take care of them."