It told investors in a global briefing note that jobs and investment on both sides of the Border could be hit – even before the 2014 referendum.
It predicted fraught divorce talks between London and Edinburgh after a Yes vote. ING said the protracted period of uncertainty cast doubt over the SNP's 2016 independence target.
The UK Government's refusal to pre-negotiate terms meant voters "are largely in the dark in terms of what they are voting for", it added.
ING said independence would have far greater economic implications than if Britain was to quit the EU.
Labour said it "shows how high the stakes are in this debate".
The Scotland Office said ING had joined "growing number of voices with concerns about independence".
However, the Scottish Government stressed a focused economic policy will be a key benefit of an independent Scotland.
A spokesman for Finance Secretary John Swinney added: "For two years – in the full knowledge we are having a referendum on independence – Scotland has been the top-performing part of the whole UK in landing inward investment jobs.
"As this paper suggests, with the full powers of an independent Scotland we can do even more to boost the economy."
The report also warned the UK Government is likely to demand strict fiscal rules and set interest rates and could force RBS to move south, while Scotland would have to reapply to join the EU and adopt the euro.