Introduction In patients with malignant pleural effusions (MPE), pleural fluid reaccumulates at variable rates following therapeutic aspiration. The aim of this study was to identify variables which predict time to next procedure and use them to develop a predictive score. Methods This prospective observational cohort study in 10 British hospitals recruited patients with known or suspected malignant effusions undergoing therapeutic aspiration. Follow-up lasted 3 months and assessed time to next clinically indicated pleural procedure. Regression analysis was performed to identify independent variables predicting time to next procedure, and a score derived. Initial validation was done in two external cohorts. Measurements and main results 241 patients were recruited. Within the derivation cohort (n=180), baseline respiratory rate (R), pleural effusion depth on ultrasound (E) and dyspnoea measured using a visual analogue scale (D) (combined to form the RED score) were independent predictors of time to next procedure. Predictive models provided areas under the receiver operator curve of 0.73 and 0.75. Initial validity testing in two cohorts (n=31, n=57) demonstrated reasonable predictive value. Conclusions In patients with MPE, baseline respiratory rate, pleural effusion depth on ultrasound and dyspnoea predict time to next procedure. Trial registration number ISRCTN16567838 .