The role of the ventromedial prefrontal cortex (vmPFC) in human pavlovian threat conditioning has been relegated largely to the extinction or reversal of previously acquired stimulus–outcome associations. However, recent neuroimaging evidence questions this view by also showing activity in the vmPFC during threat acquisition. Here we investigate the casual role of vmPFC in the acquisition of pavlovian threat conditioning by assessing skin conductance response (SCR) and declarative memory of stimulus–outcome contingencies during a differential pavlovian threat-conditioning paradigm in eight patients with a bilateral vmPFC lesion, 10 with a lesion outside PFC and 10 healthy participants (each group included both females and males). Results showed that patients with vmPFC lesion failed to produce a conditioned SCR during threat acquisition, despite no evidence of compromised SCR to unconditioned stimulus or compromised declarative memory for stimulus–outcome contingencies. These results suggest that the vmPFC...