The riot was triggered when local media broadcast news that soldiers had been sent to Uribana prison in Barquisimeto to search for weapons, Prisons Minister Iris Varela said.
Hospital director Ruy Medina told AFP news agency that some 90 people were injured, mostly from gunshot wounds.
The dead are thought to include inmates, guards and prison workers.
The director of Barquisimeto hospital, Ruy Medina, put the death toll at 54, Venezuela’s Clarin newspaper reported.
Venezuelan Human rights activist Carlos Nieto Palma said: “What should have been a normal procedure in any prison ended in a clash between National Guard [soldiers] and inmates.”
Carlos Nieto Palma added that Uribana prison was among the most dangerous in the country.
Opposition leader Henrique Capriles blamed the violence on “incompetent and irresponsible government”.
Venezuela’s prisons are blighted by overcrowding and the proliferation of weapons and drugs.
It appears that prisoners who had heard about the search in advance from news reports were waiting for the National Guard when they arrived.
It is thought that the search was aimed at disarming gangs within the prison and had been planned for some time, she reports.
There has been no official account of the incident or confirmation of the number of casualties, but the government says it will carry out a full investigation.
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