Background and purpose: Malignant pleural mesothelioma (MPM) is an aggressive cancer with a propensity for seeding procedure tracts, leading to symptomatic metastases. There is conflicting evidence on the value of prophylactic procedure tract radiotherapy in reducing tract metastases. We performed a systematic review and meta-analysis to estimate the benefit of radiotherapy in this setting. Materials and methods: Electronic databases were searched to January 1, 2018 for prospective randomized control trials with prophylactic procedure tract radiotherapy as the intervention arm. Pooled odds ratios and 95% confidence intervals were calculated using a random effects model. Study heterogeneity was assessed using the I2 statistic, and publication bias was evaluated by funnel plot and Egger's regression model. Results: Five studies were included for meta-analysis. Prophylactic radiotherapy did not have a statistically significant reduction on the risk of procedure site recurrence, with a pooled relative risk of 0.69 (95% CI 0.33–1.43). There was moderate heterogeneity between trials. All trials were assessed as moderate or high risk of bias overall. Conclusion: This systematic review has confirmed that there is no role for prophylactic procedure tract radiotherapy in MPM. In the absence of effective prophylactic procedures, patients need to be monitored closely, and palliative interventions delivered in a timely manner to reduce morbidity associated with procedure tract metastases.