In a 65-page report issued Monday, the private watchdog group argues that there are records and eyewitness testimony of "botched executions" in which prisoners might have been insufficiently anesthetized, experiencing pain but unable to signal their distress as the lethal drugs took effect.
Lethal injections are used by the federal government and 37 of the 38 states that have the death penalty, including Nevada. Nebraska still uses the electric chair.
Under the most commonly used procedure, the condemned prisoner is injected with a series of drugs: an anesthetic; a drug to paralyze the prisoner's muscles; and finally potassium chloride, which stops the heart.
In its report, Human Rights Watch said that veterinary guidelines prohibit the use of potassium chloride to put down cats and dogs because it can cause intense pain unless the animal is deeply unconscious.
The report - mentioning an issue that has been raised before in the death penalty debate - said no such precautions are taken for prisoners being executed.
In Nevada, a man convicted of raping and killing a Reno woman in her home in 1988 is scheduled to be put to death by lethal injection in Carson City Wednesday night.
Unless he changes his mind, Daryl Mack will become the 12th inmate to die in Nevada since the death penalty was reinstated.
The rights group opposes capital punishment in all forms, but said that short of an outright ban, states are required under international human rights laws to use methods that "will reduce, to the greatest extent possible, the prisoner's risk of mental or physical agony."
Anti-death penalty groups say that legal battles over the lethal injection procedure are ongoing in at least 14 states.
The Supreme Court has never addressed whether lethal injection amounts to cruel and unusual punishment.