Objective: Neuroticism, a characteristic associated with increased stress vulnerability and the tendency to experience distress, is strongly linked to risk of different forms of psychopathology. However, there are few evidence-based interventions to target neuroticism. This pilot study investigated the efficacy and acceptability of mindfulness-based cognitive therapy (MBCT) compared with an online self-help intervention for individuals with high levels of neuroticism. The MBCT was modified to address psychological processes that are characteristic of neuroticism. Method: Participants with high levels of neuroticism were randomized to MBCT (n = 17) or an online self-help intervention (n = 17). Self-report questionnaires were administered preintervention and again at 4 weeks postintervention. Results: Intention-to-treat analyses found that MBCT participants had significantly lower levels of neuroticism postintervention than the control group. Compared with the control group, the MBCT group also experienced significant reductions in rumination and increases in self-compassion and decentering, of which the latter two were correlated with reductions in neuroticism within the MBCT group. Low drop-out rates, high levels of adherence to home practice, and positive feedback from MBCT participants provide indications that this intervention may be an acceptable form of treatment for individuals who are vulnerable to becoming easily stressed. Conclusions: MBCT specifically modified to target neuroticism-related processes is a promising intervention for reducing neuroticism. Results support evidence suggesting neuroticism is malleable and amenable to psychological intervention. MBCT for neuroticism warrants further investigation in a larger study.