BACKGROUND: Malignant pleural effusion is associated with short life expectancy and significant morbidity. A randomized controlled trial comparing indwelling pleural catheters (IPCs) with talc pleurodesis found that IPCs reduced in-hospital time and the need for additional procedures but were associated with excess adverse events. METHODS: Using data from the clinical trial, we compared costs associated with use of IPCs and with talc pleurodesis. Resource use and adverse events were captured through case report forms over the 1-year trial follow-up. Costs for outpatient and inpatient visits, diagnostic imaging, nursing, and doctor time were obtained from the UK National Health Service reference costs and University of Kent's Unit Costs of Health and Social Care 2011 and inflated to 2013 using the UK Consumer Price Index. Procedure supply costs were obtained from the manufacturer. Difference in mean costs was compared using nonparametric bootstrapping. All costs were converted to US dollars using the Organisation for Economic Co-operation and Development Purchasing Power Parity Index. RESULTS: Overall mean cost (SD) for managing patients with IPCs and talc pleurodesis was $4,993 ($5,529) and $4,581 ($4,359), respectively. The incremental mean cost difference was $401, with 95% CI of -$1,387 to $2,261. The mean cost related to ongoing drainage in the IPC group was $1,011 ($732) vs $57 ($213) in the talc pleurodesis group (P = .001). This included the cost of drainage bottles, dressing changes in the first month, and catheter removal. There was no significant difference in cost of the initial intervention or adverse events between the groups. For patients with survival < 14 weeks, IPC is significantly less costly than talc pleurodesis, with mean cost difference of -$1,719 (95% CI, -$3,376 to -$85). CONCLUSIONS: There is no significant difference in the mean cost of managing patients with IPCs compared with talc pleurodesis. For patients with limited survival, IPC appears less costly. TRIAL REGISTRY: isrctn.org; No.: ISRCTN87514420; URL: www.isrctn.org.