Earlier studies on the influx of new doctors have been inconclusive
Researchers say they have found a small but statistically significant increase in the number of patients who die each year when junior doctors start work.
An Imperial College team looked at 300,000 emergency patients admitted to English hospitals between 2000 to 2008.
They compared death rates between the first week of August, when new doctors arrive, and the previous week in July.
After adjusting for various factors, they report in PLoS One that the August patients were 6% more likely to die.
The period when an influx of newly qualified doctors enters the wards has sometimes been dubbed the "killing season", but studies to establish whether there is any truth to this have been inconclusive.
The researchers from Imperial College London stressed they were unable to draw firm conclusions about the reasons for the increase, but that it was significant, if small.
Comparisons of the raw figures showed little difference, but when factors including age, sex, socio-economic deprivation and existing medical problems were taken into account, a discrepancy began to emerge.
The differences were most pronounced among medical patients - those not requiring surgery and not suffering from cancer. For this group, death rates increased by 8%.
"Our study does not mean that people should avoid going into hospital that week. This is a relatively small difference in mortality rates, and the numbers of excess deaths are very low," said Dr Paul Aylin, from the Dr Foster Unit at Imperial College.
"It's too early to say what might be causing it. It might simply be the result of differences between the patients who were admitted."
But the report notes that if these differences are due to the changeover of hospital staff, "then this has potential implications not only for patient care, but for NHS management approaches to delivering safe care".
Doctors' representatives sounded a note of caution.
"This study has to be judged alongside many previous studies looking at mortality rates before and after junior doctors start their new jobs, which have not shown any differences," said Dr Shree Datta, chair of the junior doctors' committee at the British Medical Association.
"Clearly even a small increase in death rates is of great concern and we need further research to see whether this is a real effect or an anomaly."
Hugh Williams, of Action Against Medical Accidents, said: "I think some junior doctors are thrown in the deep end and are expected to get on with it.
"It would be interesting to know how quickly this effect wears off and how different hospitals deal with the intake of junior doctors every August."
A spokesperson for the Department of Health said: "Patients should be reassured that junior doctors undergo rigorous training and they undertake direct clinical care in areas where they have been trained and assessed as meeting the required competency.
"Local hospitals must ensure that they responsibly manage the introduction of new junior doctors each August by providing appropriate senior cover and supervision."