Patients with psychopathy need intensive care and supervision. There is however reluctance to treat them because of (supposedly) limted chances of success and risk of therapy-interfering behavior. This study focused on inpatient disruptive behavior in mentally disordered offenders during medium security treatment. Patients (N = 224) were assessed using the Psychopathy Checklist-Revised total, factor and facet scores and divided into three groups depending on the presence of low, medium, and high psychopathy traits. Associations between psychopathy and criminogenic risk and need factors were analyzed. Additionally, the association between psychopathy and therapy-interfering behavior (non-compliance, drop-out, institutional misconduct) was investigated with correlational and logistic regression analyses. The results showed that psychopathy was associated with greater risk, needs, and therapy-interfering behavior. PCL-R Factor 2 predicted institutional misconduct, whereas PCL-R Factor 1 predicted drop-out from treatment. The study highlights the importance of responsive treatment climates in retaining this difficult-to-treat group in treatment.