By a wide margin of nine votes in favour and two against, the court's justices upheld the bill that legalised euthanasia and assisted suicide for people with incurable or debilitating diseases who want to end their life.
Spain is the fourth country in the European Union to have such a law.
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The court said it based its ruling on two constitutional articles guaranteeing the fundamental right to physical and moral integrity and the principles of human dignity and free development of personality, respectively.
"The Constitution protects a right of self-determination that allows individuals to make a free, informed and conscious decision on how and when to die in medically proven situations of terminal or seriously incapacitating illness," Judge Ramon Saez wrote.
Both Vox and the conservative People's Party (PP) had voted against the bill. Euthanasia is strongly opposed by the Catholic Church, whose doctrine views life as a divine gift that should not be prematurely shortened.
The PP also challenged the constitutionality of part of the law before the top court, but Wednesday's ruling effectively means it is set to be dismissed with the same arguments the court used to throw out Vox's appeal.
