The decision means no one has been prosecuted for abducting Somchai Neelapaijit, a Muslim lawyer who vanished in 2004 while he was defending suspected Islamic militants who had accused authorities of torturing them while in custody.
The unsolved case has been a stain on the law enforcement record in a country where official corruption and forced disappearances are commonplace and the police have long been accused of failing to adequately investigate themselves.
Somchai disappeared from the streets of Bangkok under the government of Thaksin Shinawatra during a surge in fighting between the army and Islamist militants in Thailand's deep south.
Thaksin, who was eventually deposed in a military coup, was on record as saying the lawyer had been killed by at least four government officials, although his body has never been found.
Five police officers eventually stood trial over the incident after eyewitnesses reported seeing Somchai bundled into a car on the night he vanished.
But the court only considered charges of robbery and coercion, not for disappearing him or murder.
Once officer was convicted and later disappeared in a landslide while the other four walked free.
In 2011, the Appeals Court ruled all five not guilty, a decision that Thailand's top court -- the Supreme Court -- upheld on Tuesday.
"The Supreme Court has agreed that (the petition) sounded unreasonable, therefore the court upheld the acquittal", one of the judges said in court.
- No family rights -
The judges also ruled that under Thai law Somchai's family has no right to bring its own civil case because there was no evidence to show he was dead or seriously injured.
"I feel very disappointed. This is a failure of the judicial process," Somchai's daughter Pratubjit told reporters outside the court.
"I would like to ask the same question I have asked for the past 10 years: where is Somchai? Where has he disappeared to?" she added.
Rights groups accuse successive Thai governments, and the country's Department of Special Investigations (DSI), of failing to get to the bottom of Somchai's disappearance.
"Seven successive Thai prime ministers have admitted government involvement and pledged action in the case of Somchai Neelapaijit, but with no tangible result," Sunai Phasuk, Thailand researcher with Human Rights Watch, told AFP.
Somchai's family had hoped a breakthrough had been made when they obtained leaked phone records from a DSI file suggesting the five officers were in close proximity to Somchai and in contact with each other on the night he disappeared.
But the Supreme Court Tuesday ruled that evidence as inadmissible because the records were photocopies and not original documents.
"We know that evidence is sitting in a folder somewhere in the DSI," Sam Zarifi, regional director of the International Commission of Jurists told AFP.
"We're back to them now. The Thai government and the DSI need to move forward with the investigation and resubmit the evidence they have."
According to the Asian Federation Against Involuntary Disappearances, there are at least 81 open cases of enforced disappearance dating back as far as the mid-1990s.
One recent case is that of Por Cha Lee Rakcharoen, also known as Billy, a rights activist campaigning for the Karen ethnic minority, who was apprehended by national park officials in Thailand in April 2014, ostensibly for illegal honey gathering. He has not been seen since.