The Hannibal Regional Hospital main campus is situated just off of Highway 36 on the west side of Hannibal, approximately 3 miles west of Highway 61. From either direction, exit Hwy 36 turning onto Shinn Lane.  Turn right on Hospital Drive, which leads to the main hospital entrance and parking lots.

Also located on the main hospital campus are the James E. Cary Cancer Center, the Hannibal Children's Center and the Shinn Lane Office Building which houses Hannibal Regional Hospital Foundation.