Ventilator weaning, the restoration of independent breathing in an individual dependent on mechanically assisted ventilation, involves gradually exposing the individual to longer periods of partially supported or independent breathing. Although ventilator weaning success is importantly related to disease or injury severity, psychological factors have been implicated in weaning outcome but remain significantly understudied. We evaluated the relationship between anxiety sensitivity (AS), an individual difference variable implicated in reactivity to stressors, and weaning success and distress in 38 mechanical ventilator-dependent patients. Equivalent evaluations were conducted with trait anxiety and depression measures for comparison. Fear of the bodily sensations associated with anxious arousal (a subcomponent of AS) and depression scores were significantly correlated with the highest level of independent ventilation achieved in early weaning trials. Fear of the bodily sensations associated with anxious arousal was significantly correlated with patient reported anxiety during weaning, even after controlling for trait anxiety and depression. Implications for the clinical management of ventilator weaning are discussed.