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The Battle of Antietam on September 17, 1862, resulted in a greater number of casualties for the regiment than any other engagement of the war. Along with other regiments of Harland's Brigade, the Eighth marched downstream from Burnside's Bridge, and crossed the Antietam at Snaveley's Ford. They proceeded up the slopes towards Sharpsburg to attack the Confederates, finally being repulsed by reinforcements under Gen. A. P. Hill at the close of the day's fighting.