Trauma Center: Under the Knife is a simulation video game developed by Atlus for the Nintendo DS. The debut entry in the Trauma Center series, it was published in Japan and North America by Atlus in 2005, and by Nintendo in Europe in 2006. Set in a near future where medical science can cure previously incurable diseases, the world's population panics when a new manmade disease called GUILT begins to spread. Doctor Derek Stiles, a surgeon possessing a mystical "Healing Touch", works with the medical group Caduceus to find a cure to GUILT. The gameplay combines surgery-based simulation relying on the DS's touchscreen controls with a story told as a visual novel.

Designed to take advantage of the DS's control options after planned development for earlier consoles stalled due to inadequate hardware, development lasted just over a year. Its early inspirations included Western television series ER and Chicago Hope, with science fiction elements incorporated during a later stage. Development proved challenging for the staff, who were veterans of the Megami Tensei franchise and had little experience with genres outside role-playing.

The game was positively reviewed by journalists, who praised the title for its use of the DS controls while criticising its difficulty spikes and repetition. While a commercial disappointment in Japan, it sold beyond expectations in both North America and Europe, boosting Atlus' profits for that year. A remake for the Wii, Trauma Center: Second Opinion, released the following year. A DS sequel, Under the Knife 2, was released in 2008.