Psychoanalytically oriented day hospital therapy, later manualized and named mentalization-based treatment (MBT), has proven to be a (cost-) effective treatment for patients with severe borderline personality disorder and a high degree of psychiatric comorbidity (BPD) in the United Kingdom (UK). As to yet it has not been shown whether manualized day hospital MBT would yield similar results when conducted by an independent institute outside the UK. We investigated the applicability and treatment outcome of 18-month, manualized day hospital MBT in the Netherlands by means of a prospective cohort study with 45 Dutch patients with severe BPD and a high degree of comorbid Axis I and Axis II disorders. Outcomes were assessed each six months. Symptom distress, social and interpersonal functioning, and personality pathology and functioning all improved significantly, with effect sizes between 0.7 and 1.7. Suicide attempts, acts of self-harm, and care consumption were also significantly reduced. The results indicate that MBT can effectively be implemented in an independent treatment institute outside the UK. This study also supports the clinical effectiveness of manualized day hospital MBT in patients with severe BPD and a high degree of psychiatric comorbidity.