Guild studied the impact of the quarantine station, and found that isolating ill soldiers and United States Navy sailors did not prevent the spread of certain diseases such as yellow fever.

The following year, he moved to the West Coast to direct the military hospital in the Presidio of San Francisco, where he was stationed when the Civil War erupted.

In July 1861, still with the rank of assistant surgeon, Guild was dismissed from the Federal army after refusing to take the oath of allegiance.

He became chief surgeon and medical director of the Army of Northern Virginia during the Peninsula Campaign in 1862 after Robert E. Lee replaced Gen.Joseph E. Johnston in command and established his own leadership staff.

During Lee's retreat following the Battle of Gettysburg in July 1863, Guild oversaw the evacuation of the Confederate wounded and their subsequent protection by cavalry under Brig.

Guild was often frustrated by the inability of the Confederate government to maintain a consistent source of medical supplies to the army in the field.