Girls were more likely to be left without a place than boys amid a surge in the number of females notably from leading private schools applying for courses in recent years.
In all, medical schools in Britain received more than 11 applications for every place last year, up from fewer than nine in 2008.
It is believed that the surge in interest for medicine is linked to rising parental pressure to secure well-paid jobs during the economic downturn particularly following a hike in tuition fees.
The Universities and Colleges Admissions Service (UCAS) said the vast majority of unplaced students were successful when they reapplied a year later.
But Mr Willetts said head teachers had a responsibility to explain the risks associated with medicine and ensure teenagers had a back-up plan.
He criticised the trend of allowing students to drop physics which is not required for medicine degrees at the age of 16 in a move that leaves many students struggling to get on to many other courses at a later date.
But the comments were attacked by private schools heads who warned that the NHS was failing to fund enough places on medical courses despite repeated complaints over a shortage of highly-trained doctors.
Mr Willetts said: There are every summer several thousand very unhappy 18-year-olds, predominately but not exclusively female, who think they will become medics who, sadly, do not get a place despite being very smart and well-qualified. And this is one of the most dysfunctional features of the English school leaving A-level system.
He added: The truth is that the number of young people - and it does tend to me more girls than boys - with an aspiration to do medicine way exceeds any number of places that the NHS is likely to have.
Previously, the number of students winning places on every degree course was closely capped by the government.
Read the original:
Willetts warns over surge in demand for medicine degrees
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