Dr Foster rated infection rates, surgery errors, deaths and staffing levels
One of 12 NHS trusts rated as "significantly underperforming" by monitoring body Dr Foster has described the methodology used as "unclear".
Lewisham Hospital NHS Trust was rated as England's third worst trust for patient safety measures by Dr Foster.
The south London trust was "surprised and disappointed" by the findings.
It said: "The methodology used to calculate this patient safety score is unclear and very difficult for the public to understand."
The part-private, part-NHS Dr Foster Hospital Guide rates trusts based on analysis of a range of "safety indicators", including infection rates, errors in surgery, deaths and staffing levels.
Lewisham Hospital NHS Trust was one of 12 hospital trusts to receive the lowest rating, including South London Healthcare NHS Trust, based at Sidcup in Kent.
A statement released by Lewisham Hospital NHS Trust said: "We are surprised and disappointed at this scoring from Dr Foster, especially as we were rated in the Top 40 Hospitals by (healthcare information firm) CHKS earlier this year."
It added: "Lewisham Hospital prides itself on patient safety. It is our top priority and is the first agenda item at every board meeting.
"We consistently have one of the lowest hospital acquired infection rates in the country and our quality of service has been rated as 'good' by the Care Quality Commission."
LOWEST RATED TRUSTS
Coventry and Warwickshire
St Helens and Knowsley
Blackpool, Fylde and Wyre
Basildon and Thurrock
Scarborough and North East Yorkshire
Source: Dr Foster Hospital Guide
The trust said it had raised concerns about the methodology used with Dr Foster.
It added: "Out of the 34 indicators, 31 were within the expected range, two were better than expected and only one was worse than expected.
"This related to the administration of the reporting of safety incidents to a national body and has no impact on patient safety at this hospital."
South London Healthcare NHS Trust was not available for comment.
After the publication of the Dr Foster Hospital Guide, the Care Quality Commission said it saw no need to intervene to make improvements.