More than half of epilepsy sufferers on disability benefits in Kirklees had their claims denied after the roll-out of the new system, figures reveal.
Charity Epilepsy Action says the system is "failing people with epilepsy", and that assessors frequently have little understanding of the condition.
Since 2013, the Government has been moving claimants from the Disability Living Allowance to the Personal Independence Payment.
Over the last six years, 247 epilepsy sufferers in Kirklees applied to switch from DLA to PIP, according to Department for Work and Pensions figures.
Of those, 126 had their claims denied and their payments stopped - 51% of applicants.
The rejection rate for epilepsy patients is almost double the average across all disabling conditions, which is 28%.
This trend is reflected across England, where epilepsy patients are almost twice as likely to be denied PIP.
Epilepsy is a serious neurological condition, but can be "fluctuating and largely invisible", according to Epilepsy Action.
A survey by the charity revealed that nine in 10 sufferers felt that the person carrying out their PIP assessment did not understand their illness.
Chief executive Philip Lee said: "Time and again, we hear that the assessment process for PIP fails to recognise the impact epilepsy can have on a person's life.
"Without PIP, many are unable to afford the adaptations they need to make in order to live a safe and independent life.
"This is a seriously flawed system that must change, or it will continue to have more devastating effects on people with epilepsy."
Anti-poverty charity Turn2Us said that the different assessment criteria for PIP can put epilepsy patients at a disadvantage.
DLA is awarded when people need supervision to keep safe, which covers epileptic seizures, whereas PIP is focused on whether someone needs help achieving specific tasks, such as preparing food, washing and dressing.
In addition, applicants will generally only satisfy a PIP criteria if it applies to them more than half the time, which is rarely the case with seizures.
Anna Stevenson, welfare benefits specialist at Turn2Us, said: "PIP assessments have come under criticism due to doubts about the capabilities of the 'health professionals' carrying out assessments, who tend to have little or no expertise in the medical condition they are assessing.
"This can lead to an inadequate understanding of a claimants needs."
The DWP said that PIP was introduced because the previous system was "outdated".
A spokesperson said that of those people with epilepsy who are awarded PIP, 27% get the highest level of support, compared to 6% under DLA.