The latest annual accounts of the national jobs quango disclose £9,460,000 of public money was lost on 60 separate write-offs in the last financial year.
The bill was more than double that of the previous year, and more than the worst previous record, of £9,327,000, in 2010-11.
Scottish Enterprise said financial support to fledgling firms and new technology companies was "high risk" by its very nature, and that the money was "no longer recoverable".
It also said some of the write-offs related to tenants not paying their rent - a hazard faced by all landlords.
The losses coincided with the first year in which a Scottish Enterprise chief executive, currently Lena Wilson, divided her time between the Government quango, which pays her £200,000, and a controversial outside job.
A non-executive director since July 2012, Wilson, 49, currently earns £58,000 a year for working one day a month for London-based Intertek Group plc, making her the first Scottish Enterprise chief to take on a second post.
In March, the Sunday Herald revealed Intertek, which runs industrial testing laboratories worldwide, paid almost no UK corporation tax in the past decade, despite gross global operating profits of £1.4 billion, adding to calls for Wilson to quit.
The Scottish Enterprise accounts to March 31, 2013, show there were six separate write-offs of more than £250,000 in the financial year 2012-13, including £3.3m lost in shares and loans with the laser technology firm, Intense Limited.
Investments and grants for the Livingston-based technology firm Elonics Ltd accounted for another £2.2m in losses, after the company was put into liquidation.
And £709,000 was lost after Scottish Enterprise invested taxpayers' cash in the Stirling-based 110 Sport Group, whose clients once included the snooker player Stephen Hendry, to help it promote snooker in China.
The accounts also show 2012-13 was the worst year for the average level of "claims abandoned or waived", with the average write-off being £157,700.
This compares to an average loss of £101,400 in the previous worst year of 2010-11, and an average loss of £51,000 in the years 2006 to 2012.
Tory enterprise spokesman Murdo Fraser said: "Unfortunately, Scottish Enterprise has a history of making a loss on large sums of taxpayers' money.
"I applaud ambitious programmes, and I accept on occasion risks will be taken with public money which do not pay off.
"But where we have such large sums of public money involved, it is important that we understand exactly what went wrong, not least so we can learn lessons for the future.
"Scottish Enterprise has to show some accountability by providing a detailed account of what went wrong with these investments."
Iain Scott, chief financial officer at Scottish Enterprise, said: "Context is important here - the value of last year's write-offs relate mainly to two companies which went into administration.
"This should be balanced against a return of £12.6m from the sale of shares, loan repayments, interest and dividends as well as £260m of private-sector investment from our RSA grants and equity investment funds last year alone."