Malignant pleural effusions cause significant morbidity, but there is no gold standard minimally invasive treatment. A new therapeutic approach combines talc pleurodesis and indwelling pleural catheters (IPCs) to enable outpatient management. This case series summarizes the safety and efficacy data of all patients (24) with a symptomatic malignant pleural effusion who underwent talc pleurodeses via IPCs between December 2010 and July 2013. Successful pleurodesis was achieved in 22 procedures (92%). There was one empyema, one hydropneumothorax, one recurrent effusion, and two minor complications: one drain site wound infection and one complaint of chest pain. Twenty-two procedures (92%) were performed in the outpatient setting. This report confirms the safety and efficacy of administering talc slurry through IPCs in an outpatient setting. Studies in a larger cohort are necessary to define the role of this novel approach in the treatment algorithm of patients with this condition.