Background: Malignant Pleural Effusion (MPE) is defined as an accumulation of pleural fluid in which malignant cells are present. It is a poor clinical indicator as it represents an advanced stage neoplasm with median survival ranging from one to 12 months. Aim: We aimed at comparing Thoracoscopic Talc Insufflation with tube thoracostomy talc slurry pleurodesis in regard to the efficacy and complications in patients with MPE. Patients and Methods: 128 patients with MPE were divided into two groups, 64 in each. One group had tube thoracostomy talc slurry (TS) pleurodesis while the other had thoracoscopic talc insufflation (TTI) pleurodesis. Results: Talc slurry was associated with a longer hospital stay. Complications recorded included chest pain (TS 29%, TTI 25.4%), dry cough (TS 16%, TTI 39%), vomiting (TS 29%, TTI 13.6%), tachycardia (TS 16.13%, TTI 18.64%), surgical wound infection (TS 11.29%, TTI 10.17%), and respiratory failure complicating talc pneumonitis (TS 3.23%, TTI 0%). Pleurodesis success was enhanced by the presence of lung cancer (OR 2.34, p=0.02) or breast cancer (OR 2.55, p= 0.03) as the primary malignancy, the younger the patient's age at pleurodesis time (OR 1.004, p=0.89) and the higher the pleural fluid glucose content (OR 1.01, p=0.09). Pleurodesis failure was strongly correlated to the presence of any of the pre-procedural factors, female gender, hepatocellular carcinoma as the primary malignancy, and low pH pleural fluid. Conclusion: In MPE patients with no evidence of lung trapping, talc pleurodesis method used should depend on local expertise (availability of thoracoscopy), whether additional tissue is needed for molecular-marker analysis (would favor thoracoscopy), plus patient-related factors (operable or not). However, TTI has a significant irrefutable benefit in patients with adhesions and trapped lung.