Ayman al-Zawahri said in a videotape broadcast by Aljazeera on Sunday that the "new Crusader campaign" would end in defeat as others had in the past.
Al-Zawahri, wearing a white turban and seated with a machine gun next to him, said his comments came three years after the first prisoners were taken from Afghanistan to the US naval base at Guantanamo Bay, Cuba.
"If you Western nations believe that these cartoon governments will protect you from our responses, then you are deluded. Your real security lies in cooperating with the Islamic nation on the basis of respect and ending aggression," al-Zawahri said.
"Your new Crusader campaign will end, God willing, in defeat as did those that preceded it but after the deaths of tens of thousands, the destruction of your economy and exposing you in the pages of history," he added.
Al-Zawahri said US calls for democracy in the Middle East were a farce after allegations of abuse of prisoners in Iraq, Afghanistan and in Guantanamo Bay, which holds hundreds of suspects detained during the 2001 US-led war to oust al-Qaida and the ruling Taliban from Afghanistan and in other operations.
"It has been three years since the first group of Muslim prisoners were sent to Guantanamo prison... One may ask why all this interest in Guantanamo when our countries are filled with a thousand Guantanamos under US observation," he said.
Al-Zawahri and Usama bin Ladin
have eluded the US dragnet
"It is because it exposes the truth of reform and democracy that America claims it aims to spread in our countries.
"The reform which emerges from US prisons like Bagram, Kandahar, Guanatanamo, Abu Ghraib, and from the launch of cluster bombs and rockets and the appointment of the likes of [Afghanistan's President Hamid] Karzai and [Iraqi interim Prime
Minister Iyad] Allawi," he said.
Al-Zawahri and al-Qaida chief Usama bin Ladin, believed to be hiding in the border region between Pakistan and Afghanistan, have eluded capture since the 11 September 2001 attacks on the United States, claimed by al-Qaida.
The last videotape from al-Zawahri - aired in November - warned that al-Qaida would continue to attack the US until Washington changed its policies towards the Muslim world.
In Washington, a US intelligence source said it was too early to make a determination on the tape's authenticity, adding: "We will certainly be looking very closely at it."