Iain Duncan Smith has warned Scottish voters that an independent Scotland would see its bill for benefits and pensions soar.
The work and pensions secretary said that analysis by his department showed that SNP policy pledges and the impact of an ageing population would add about £450 more per working-age person each year over the next two decades.
The total includes £410 more spending on pensioners and £40 more on workers.
The predictions, set out in the latest "Scotland analysis" paper, follow claims by former prime minister Gordon Brown that the pensions bill would be three times the income from oil.
The Scottish Government accused Westminster politicians of scaremongering while cutting an estimated £6 billion from welfare north of the border.
Duncan Smith said: "This country has a long history of a strong welfare state, which we can rightly be proud of.
"As part of the UK, Scottish people benefit from this resilient and unified system, which delivers the same support everywhere irrespective of peaks and troughs in economies of the nations or demographic differences.
"Proposals by the Scottish Government would risk the well-being of vulnerable people who are currently supported by this system.
"On top of the ageing population, which is increasing faster in Scotland than the rest of the UK, the Scottish Government are committing to spending even more on wider welfare without saying how they'll pay for it."
Scotland's benefits bill, including childcare and tax credit, totalled £17.7 billion in 2012-13. Spending was £60 more per person than in the UK as a whole, according to the report.
The UK Government also points to the higher proportion of pensioners in Scotland, which stands at 19.8% compared with 19.2% in the rest of the UK.
The share will rise faster north of the border by the early 2030s, official projections suggest.
Spending on pensioner benefits in Scotland costs almost £80 more per working-age person per year than across the UK.
Alistair Carmichael, the Scottish Secretary in the UK Government, said: "The UK labour market is resilient, adaptable to changes in economic conditions and responsive to new opportunities and challenges.
"As part of the UK, Scotland benefits from the policies that have created these conditions.
"Both the UK and Scotland have flexible labour markets with a wide variety of jobs and working patterns available.
"With record employment in our country, people can move across other parts of the UK, to where there are labour shortages or where to find a job that better matches their skills, ambitions and aspirations."
Scotland's Deputy First Minister, Nicola Sturgeon, criticised the UK Government analysis.
She said: "Welfare spending and pensions are more affordable in Scotland than the UK because they account for a smaller proportion of our tax revenues and national income.
"But now a Tory-led government that Scotland didn't vote for is dismantling large parts of the post-war welfare state because of its right-wing ideology.
"This is social vandalism on a vast scale and shows why people are worse off when decisions about Scotland are taken at Westminster."
She said Duncan Smith is afraid to come to Scotland to launch the analysis paper in person - and is using Carmichael as a "human shield". Sturgeon added: "Perhaps he is aware of the hypocrisy at the heart of their message today."
The independence referendum will be held on September 18.