Background: While short-term psychodynamic psychotherapies have been shown effective for major depression, it is unclear if this could be a treatment of choice for depressed patients, many of whom have chronic and complex health issues, who have not sufficiently responded to treatment. Method: This superiority trial used a single blind randomised parallel group design to test the efficacy of time-limited Intensive Short-Term Dynamic Psychotherapy (ISTDP) for treatment resistant depression (TRD). Patients referred to secondary care community mental health teams (CMHT) who met DSM-IV criteria for major depressive episode, had received antidepressant treatment weeks, and had Hamilton Depression Rating Scale (HAM-D) scores of were recruited. The effects of 20 sessions of ISTDP were judged through comparison against secondary care CMHT treatment as usual (TAU). The primary outcome was HAM-D scores at 6 months. Secondary outcomes included the Patient Health Questionnaire (PHQ-9) self-report measures for depression and dichotomous measures of both remission (defined as HAM-D score <= 7) and partial remission (defined as HAM-D score <= 12). Results: Sixty patients were randomised to 2 groups (ISTDP = 30 and TAU = 30), with data collected at baseline, 3, and 6 months. Multi-level linear regression modelling showed that change over time on both depression scales was significantly greater in the ISTDP group in comparison to TAU. Statistically significant between-group treatment differences, in the moderate to large range, favouring ISTDP, were observed on both the observer rated (Cohen's d=0.75) and self-report measures (Cohen's d=0.85) of depression. Relative to TAU, patients in the ISTDP group were significantly more likely after 6 months to achieve complete remission (36.0% vs. 3.7%) and partial remission (48.0% vs. 18.5%). Limitations: It is unclear if the results are generalizable to other providers, geographical locations and cultures. Conclusions: Time-limited ISTDP appears an effective treatment option for TRD, showing large advantages over routine treatment delivered by secondary care services.