The work, which uses 2013 GCSE results to model the effect of upcoming reforms to school accountability measures, suggests that the number of secondaries failing to meet minimum standards will increase by 72 per cent.
Hundreds could face government intervention, takeover or even closure unless they make changes to take account of the new Progress 8 (P8) league table measure, which comes into effect in 2016.
The research was carried out by the Fischer Family Trust (FFT), an independent charity that provides school data analysis to the government. It includes all state secondaries that were open in England in the summer of 2013 and shows that 189 of them failed to meet the current "floor standard" of at least 40 per cent of pupils gaining five A*-C GCSEs or equivalent, including English and maths (5ACEM).
But when the results from that year were measured against the P8 target - which looks at the progress pupils make in relation to prior attainment across a broader range of eight subjects - 325 schools failed to achieve the minimum standard.
The analysis also suggests that the new regime will shift the focus away from many schools who are currently seen as having unacceptably low standards and on to others that have not previously been regarded as failing.
Mike Treadaway, research director for the FFT, said: "It suggests that Progress 8 will bring about substantial changes. Some schools will be below the floor when they have never been anywhere near before, but others, maybe for the first time, will be seen as making good progress with their pupils rather than `failing'."
Of the 325 secondaries shown to have fallen below the new P8 target, 145 had GCSE grades high enough to be above the current floor standard.
The FFT does not reveal the identities of the schools in the analysis, but one of them did not meet the new progress standard even though 98 per cent of its pupils achieved 5ACEM. It is one of 35 schools that would miss the new target despite more than half their pupils reaching the current GCSE benchmark.
Dr Treadaway said that the 145 secondaries on course to slip below acceptable standards were "in the main, schools where intake is average or higher [in terms of prior attainment] but pupils make relatively low progress".
Poor progress among more-able pupils during secondary school can be masked by the main current performance measure because this only looks at whether pupils have crossed the CD grade threshold. The new system will give schools credit for all progress made at all grades.
"At last we are recognising some schools that have maybe not been thought of that brilliantly, but actually do a decent job," Dr Treadaway said. "Maybe some schools that have been over-focusing on one group of kids because of government pressures might have to work on that."
His analysis also takes into account another league-table change, which, from this year, limits the number of vocational qualifications that qualify and reduces their equivalence from multiple GCSEs to just one each.
Based on the 2013 results, this would have left 355 secondaries below the current floor standard. But if the new progress measure is applied, 175 of them are lifted above the floor.
"Quite a few of these will be schools with relatively low prior-attaining intakes, which are doing a reasonably decent job in terms of progress," Dr Treadaway said. "When you take intake into account, which Progress 8 does, they suddenly look a lot better."
Russell Hobby, general secretary of the NAHT headteachers' union, said: "I suspect that the shift towards a progress measure ought to help schools serving more challenging communities with lower attainment on entry a great deal.
"But a lot of schools are going to find that some of their old assumptions about what worked and what propelled them up the league tables are going to change quite dramatically."
Brian Lightman, general secretary of the Association of School and College Leaders, said: "We think Progress 8 is a better measure but we remain concerned about the use of accountability measures to drive curriculum change."
The Fischer Family Trust will be running Progress 8 training events this autumn to help schools prepare for the changes.
Read a full analysis of the report
`It is a zero-sum game'
David Blow, headteacher of Ashcombe School in Surrey, currently has 71 per cent of pupils achieving five A*-C GCSEs including English and maths, placing the comprehensive well above the minimum floor standard.
He uses a GCSE-based, rather than a vocational, curriculum. But Mr Blow says he is still not confident of a good result on the Progress 8 measure because it depends on schools' performances in relation to each other.
When asked what his score would be, Mr Blow says: "Nobody can tell. It depends totally on the behaviour of other schools in the country.
"It is a zero-sum game and we know that other schools have already started optimising their curriculum to meet Progress 8.
"We have consciously decided to make no changes. Our governors say it is more important for our pupils to be getting the right education rather than chase an Ofsted outstanding grade."
Mr Blow believes the school has made the correct decision but is concerned about league tables because "I don't know where we are going to end up".