Abstract Purpose To determine the objective response rate of malignant pleural mesothelioma (MPM) to short course radiation therapy. Methods We reviewed the cases of 54 patients with advanced MPM who were treated with palliative radiotherapy according to a standardised institutional policy. Pre- and post-treatment computed tomography scans were used to assess response. Results Fifty-seven percent of patients reported some improvement in their symptoms following radiotherapy. The radiology response rate was 43% (22 patients had a partial response and 1 patient a complete response). Response to treatment was correlated with the European Organisation for Research and Treatment of Cancer (EORTC) prognostic index (p=0.001), performance status (p=0.02) and histological subtype (p=0.04). In the EORTC good prognosis group 56% of patients responded, compared with only 7% in the poor prognosis group (p=0.001). The median survivals from diagnosis and from the start of radiotherapy were 11.3months and 5.2months, respectively. Survival following treatment was correlated with the EORTC prognostic index (p<0.001), histological subtype (p<0.001), performance status (p=0.001), treatment response (p=0.002) and haemoglobin level (0.02). The EORTC good and poor prognostic groups had survivals of 7.1 and 2.1months, respectively (p<0.001). Neither tumour volume nor stage were associated with prognosis. Conclusions Palliative radiotherapy produces a response rate in MPM that is equivalent to chemotherapy. The EORTC prognostic index can be used to select patients who are most likely to benefit from this treatment.