Twomile Run is a tributary of Kettle Creek in Clinton County, Pennsylvania, in the United States.

Twomile Run begins in Sproul State Forest in Leidy Township, Clinton County.

Soon after entering Noyes Township, it receives the tributary Middle Branch Twomle Run and continues south.

Shortly after the final bend, it receives the tributary Huling Branch and not long afterwards enters Kettle Creek.

[5] The watershed of Twomile Run experiences significant acid mine drainage, with 2.3 miles (3.7 km) of the stream being affected by it.

The stream is the only significant source of acid mine drainage to enter Kettle Creek on its eastern side.

[4] Thirty to fifty percent of the acid mine drainage in the Twomile Run watershed comes from baseflow.

[4] The manganese concentration at the mouth of Twomile Run ranges from 2.1 to 11.7 milligrams per liter.

[4] Upstream of Middle Branch Twomile Run, the concentration is 6.83 milligrams per liter and the daily load is 57.0 pounds (25.9 kg).

Above Pecking Patch Hollow, the concentration of manganese is 6.43 milligrams per liter and the daily load is 119.2 pounds (54.1 kg).

Downstream of Huling Branch, the manganese concentration is 6.44 milligrams per liter and the load is 296.0 pounds (134.3 kg) per day.

The load of acid above Middle Branch Twomile Run is 205 pounds (93 kg) per day.

The concentration of alkalinity in Twomile Run upstream of Pecking Patch Hollow is 1.03 milligrams per liter.

[5] The sulfate load upstream of the swamp on Twomile Run is 51 pounds (23 kg) per day and upstream of Middle Branch Twomile Run, the daily load is 1,207 pounds (547 kg).

[4] The sediment load in the Twomile Run watershed is 0.38 pounds (0.17 kg) per acre per year.

[4] The velocity-depth of Twomile Run is low, but there is an adequate frequency of riffles in the stream.

[4] Most of the land in the watershed is owned by the Pennsylvania Department of Conservation and Natural Resources, the Bureau of Forestry, and Sproul State Forest.

[7] In the 1930s and early 1940s, there was a Civilian Conservation Corps located in the Twomile Run watershed.

[11] A draft for an Operation Scarlift report was written in 1973 for Kettle Creek (which Twomile Run is a tributary of), but was never approved.

[4] Brook trout are found in the upper reaches of the tributary Middle Branch Twomile Run, upstream of the acid mine drainage discharges in its watershed.

[4] The stonefly and caddisfly populations on Middle Branch Twomile Run are increasing.

The Pennsylvania Fish and Boat Commission assessed the mouth of the stream as 2 out of 10 on their habitability scale in the same year.