The basic course of gameplay for Second Opinion is the same as from the original DS game. Refer to Trauma Center: Under the Knife for further details.

In the game, the player uses the Wii Remote and the Nunchuk attachment to play instead of the DS stylus. Most of the tools are used with the Wii Remote while the Nunchuk allows players to quickly switch between instruments. As well as having all of the tools from Under the Knife at the player's disposal, the player can also make use of a few situational tools. Some of the existing tools have added functionality from the previous game.

Other than the new functionality, the main objective of the game remains the same as the DS version. Your goal is to treat whatever is wrong with the patient in the alloted time limit without letting the patient's vitals reach 0 or making too many mistakes. The game will initially give you basic missions to let you get used to the game, but as you progress, you will encounter the GUILT from the previous game, which are mostly dealt with in the same manner with a few exceptions in later missions.

Tools With New Functionality
Magnifier, Drain, Syringe: None of these have any new purposes, but they are now operated by simply pressing or holding the A button.
Scalpel: In the bomb mission, it's used to remove screws from the casing.
Forceps: To hold onto something, you have to hold the A and B buttons, as if actually pinching a pair of forceps. Can also rotate objects while they're held. Also takes forward-back motion into account.

New Tools
Defibrillator: Used when a patient is suffering from Cardiac Arrest. Replaces the Gel and Massage method from the DS version. Push the Wii Remote and Nunchuk towards the screen, which will make a gauge appear. Try to stop the bar in the green by pressing B and Z at the same time.
Penlight: Used in Nozomi's third mission to illuminate dark areas. Has to be moved around to see what you are doing.
Flash Camera: Also used in Nozomi's third mission: Its flash provides the same effect as the Penlight, but has to be reused when the light fades.

Healing Touch
Both Derek and Nozomi have the ability to use the healing touch, but what it does is different between the two of them. While Derek is still able to use his concentration to seemingly slow down time for him, Nozomi's abilities allow her to heal the patient when getting "Ok", "Good", or "Cool" when fixing a patients wounds. Like in the DS version, Healing Touch is activated by drawing a star on the screen, and how well the star is drawn has an effect on how much time you're given.

GUILT
While your encounters with the man-made GUILT will be mostly the same, the later in the game you will be presented a few unique dealings with GUILT. A few situations in the game will give you the task of having to deal with multiple types of GUILT at the same time, such as Kyriaki and immature Savato and even an enhanced version of Savato.

Spoiler warning: Plot and/or ending details about GUILT in Second Opinion follow.

The GUILT, Triti, does not require cutting after the thorns are removed to remove it.
"Sayonara" involves removing Kyriaki while trying not to kill immature Savato.
"Relapse" features a strain of Tetarti that only show their colors through the toxins they emit.
"Second Opinion" has Dr. Stiles infected with both Kyriaki and smaller Paraskevi, which are initially at his heart.
"Fallen Heroes" is similar to "Under The Knife", only the player has to remove Triti, Kyriaki, Deftera, and Paraskevi.
"Vulnerabilities" has Director Hoffman infected with a much stronger form of red-colored Savato that moves across portions of the heart.

Game Sequence
For the most part, Second Opinion's levels are the same as they were in Under the Knife. However, completing each chapter in Dr. Stiles' game unlocks a chapter in Dr. Weever's stage, which are referred to as Z-1, Z-2, and so on up to Z-5. The sixth chapter brings the two doctors together to take the new operations.

Italics indicates the name was changed from the DS version, bold indicates a new chapter