And it ranks 179th overall in the UK.
The parliamentary constituency area, which includes Clydesdale and Tweeddale, has 3890 small businesses operating from it.
The Dumfries and Galloway area is slightly behind at 14th overall in Scotland and 253rd in the UK, with 3855 small businesses located there.
The study by Nimble Fins used data from the Office of National Statistics and was based on the number of VAT/PAYE based enterprises in region. Further information can be found at www.nimblefins.co.uk/business-insurance/which-areas-UK-most-entrepreneurs.