Obama argued there are some crimes so heinous that capital punishment could be merited, but warned the incident on Tuesday raised "significant questions about how the death penalty is being applied."
Clayton Lockett, a convicted murderer and rapist, was administered a new, untested three-drug protocol.
He died 43 minutes after the start of the injection -- the process usually takes 10 minutes -- prompting allegations of torture.
"What happened in Oklahoma is deeply troubling," Obama admitted during a joint White House news conference with visiting German leader Chancellor Angela Merkel.
"And I've said in the past that there are certain circumstances in which a crime is so terrible that the application of the death penalty may be appropriate -- mass killings, the killings of children.
"But I've also said that in the application of the death penalty in this country, we've seen significant problems. Racial bias.
"An uneven application of the death penalty. Situations in which there were individuals on death row who later on were discovered to have been innocent because of exculpatory evidence.
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