Being admitted to hospital with internal bleeding on a bank holiday pushes up the risk of dying by 41%, researchers have said.
Inadequate staff cover and a lack of access to hospital tests means patients are more likely to die than those admitted on week days.
Admission on a weekend also increases the risk of death by 13%.
The research, by experts at the University of Swansea, looked at admissions for upper gastrointestinal (GI) bleeding, which can be caused by a range of conditions including ulcers and gastritis.
It confirms other studies, which show a higher chance of dying if a person is admitted to hospital on weekends.
In June, a review found that the death rate among NHS emergency admissions across England increased by 7% at weekends in 2005-06.
That is the equivalent of 3,369 more deaths at the weekend than would normally be expected.
Experts said one reason was a lack of consultants and fewer specialist services available at the weekend, including diagnostic tests.
And last week, the Royal College of Physicians (RCP) warned that patients are being left in the hands of junior doctors because of inadequate consultant cover on weekends.
The study, published in the journal Alimentary Pharmacology and Therapeutics, analysed more than 24,000 admissions for upper GI bleeding between 1999 and 2007 in Welsh hospitals, including emergency admissions.
Lead author Dr Stephen Roberts said: “The higher death rates for weekend and public holiday admissions could not be explained by differences in the patients admitted and may be down to reduced staffing levels or delays in investigative procedures such as endoscopy (an internal examination).
“It is very clear from our research that further studies are needed to understand why death rates are much higher at weekends and on public holidays than during the week.”
Dr Roberts said fewer staff and a lack of consultants could lead to numerous issues, including less rigorous assessments, poor communication at handover meetings and delayed investigations.
Andrew Goddard, director of medical workforce at the Royal College of Physicians, said: “This study provides yet more evidence that patients in hospital are not cared for so well at weekends, and reinforces last week’s call from the RCP for physicians caring for very sick patients to be in the hospital for 12 hours a day, every day, including weekends.
“The RCP, with other organisations, will shortly be launching a toolkit for hospitals to assess, treat and manage upper gastrointestinal bleeding, which will help to prevent unnecessary deaths in the future.”
A spokesman for the Department of Health said: “Patients deserve better care at night and weekends, and senior doctors should be available to provide medical care as needed.
“The Secretary of State for Health has already asked Medical Education England to consider with the profession, the service and medical Royal Colleges how best to secure better patient outcomes and the right level of supervision for trainees through greater consultant involvement in direct clinical care at night and at weekends.”