A review team says it is alarmed that some trainee doctors do not have adequate supervision.
The inquiry into how young doctors spend their first two years in the NHS said the issue must be urgently addressed.
The review team, who spoke to junior doctors across England, heard about a trainee being left in charge of 100 patients overnight and at weekends.
Health Secretary Andrew Lansley has asked for quick action on the report.
Doctors' training has been a controversial area since changes to the application system caused uproar in 2007.
This review was ordered to look at trainees' roles in the two-year foundation programme in England, and how they are regulated.
The team of 14 experts spoke to junior doctors in big cities around England and looked at evidence from a range of other sources.
Patients 'at risk'
Chairman Professor John Collins said: "Many exciting things have been done to help these young people integrate into clinical practice.
"But we also found worrying features - particularly newly qualified doctors employed outside their level of competence and without appropriate supervision.
"We were given alarming evidence of unacceptable practise.
"One example was a young doctor who told us she had recently qualified. She was left to look after 100 very sick patients at nights and weekends without appropriate cover.
"That is completely unacceptable. It puts patients at risk and gives these young post-graduates the wrong message that sub-optimal care is condoned.
"It is difficult to gauge how common it is, but over and over again we heard this message about being asked to fill rosters or attend to patients beyond their level of competence.
"Even if it is a small number, we must address this."
Prof Collins said in some cases trainees were being failed by hospital systems, but in other instances they weren't getting adequate supervision from consultants.
The report also recommends that the curriculum for junior doctors has an increased emphasis on managing chronic illness.
Dr Tom Dolphin, co-chairman of the British Medical Association's junior doctors committee, said: "It is incredibly stressful for doctors to be put in this position and it will inevitably threaten patient safety.
"Our medical education system produces highly skilled graduates, but they must be properly supported once they begin direct patient care.
"We also need to urgently investigate problems with the selection of doctors into the programme, the length of work placements and the excessive levels of assessment."
Mr Lansley praised the report as "thorough".
He said: "I have asked Medical Education England to work with the profession, the service and medical royal colleges to take forward the recommendations as swiftly as possible.
"This will fit with Medical Education England's ongoing work to improve the quality of training, ensuring that trainees have appropriate supervision and are not undertaking tasks for which they are not yet competent."