Managing Cancer and Living Meaningfully (CALM) is a brief, evidence-based psychotherapy tailored for patients with advanced cancer that has not yet been implemented routinely in Dutch cancer care. The aim of this study was to assess the feasibility, acceptability, sustainability and effectiveness of CALM in different clinical settings in the Netherlands. In 2019 and 2020 a multi-center, intervention-only study was performed in three Dutch cancer care settings. Professionals were trained to provide CALM under supervision. Patients diagnosed with advanced cancer were included and filled out questionnaires to measure depression (Patient Health Questionnaire-9), death anxiety (Death and Dying Distress Scale), and anxiety (hospital anxiety and depression scale-anxiety) at baseline, 3 and 6months. The Clinical Evaluation Questionnaire was used to assess acceptability of CALM at 3 and 6months. Sixty-four patients (55% of the eligible patients) were included in the study and 85% of the included patients received 3 or more CALM sessions. Of the 24 trained therapists, 15 (63%) started providing CALM. Two years post-study, CALM was provided in each center by a total of 19 therapists. On average, patients perceived CALM to be at least somewhat helpful. A significant decrease in severity of depression (p=0.006), death anxiety (p=0.008), and anxiety (p=0.024) was observed over time. This study shows that CALM therapy is feasible, acceptable, and sustainable in three Dutch cancer care settings, although not all predefined feasibility criteria for therapists were met. CALM can be effective in decreasing feelings of depression, anxiety, and death anxiety in patients with advanced cancer.