Patients failed to attend nearly 130,000 hospital appointments in Leeds last year.
And over three years, the number of appointments where patients did not turn up or cancelled on the day topped 368,000.
The cost to the NHS in Leeds is estimated at around £21m last year alone.
Since 2010, that cost could rise to as much as £62m.
In the city the “did not attend” (DNA) rate for hospital outpatient appointments was 12.2 per cent, higher than the national average of 7.3 per cent.
Hospital bosses said the problem was a “significant waste of NHS resources”.
According to figures obtained under the Freedom of Information Act, the number of DNAs increased from 120,826 in 2010 to 127,699 in 2012/13.
The greatest proportion of missed appointments was in Critical Care, where last year in nearly half of all outpatient appointments, patients did not turn up.
That was followed by haemophilia clinics, where over a third of patients failed to attend.
As the average cost of an outpatient appointment is £170, the cost of the missed dates could run into millions in Leeds.
The figures were revealed less than two months after health bosses in Leeds warned health and social care in the city could face a £250m shortfall within two years.
A spokesman for Leeds Teaching Hospitals NHS Trust said: “When patients do not attend a booked appointment this is a significant waste of NHS resources and it is important to keep these occurrences to a minimum.
He said they could be caused by a number of reasons, including patients moving or changing GP but not telling the hospital.
“The trust does have checking mechanisms – including following up mail which has been returned through the post as undeliverable – but we would urge patients to help us by notifying us of their new details as soon as possible,” he added.
He added that newly-introduced self check-in kiosks for patients queried whether details were corrected and they hoped this would help pick up errors.
New voice and text message reminders a week before appointments are also being used.
“Early indications are that this is delivering a reduction in DNA rates,” the spokesman added.
“We do understand that circumstances can change after appointments are made but if patients contact us in good time once they know they cannot attend we can both re-book a new appointment and allocate their slot to another patient.”
The spokesman said that anyone who could not attend an appointment on the date requested should ring the number on their appointment letter.