Card Sound Road reopened shortly before midnight Monday into Tuesday morning, according to the Monroe County Sheriff's Office.
The road had been closed due to a brushfire near the Miami-Dade County line that had been affecting traffic since Sunday.
Should the fire flare up again, motorists must use the 18 Mile Stretch to get in and out of the Keys. The sheriff's office is posting updates via its Twitter and Facebook accounts.
While Card Sound Road was closed, travelers from the mainland to Ocean Reef in North Key Largo, travelled down the 18-Mile Stretch to Key Largo to get on State Road 905 near Mile Marker 106.5, to travel north to Ocean Reef. The reverse route was required when leaving Ocean Reef to travel to the mainland.