The current work was aimed to develop Medium Chain Triglyceride (MCT) rich self nanoemulsifying preconcentrate of paclitaxel (PTX) for parenteral delivery. Very high concentrations of Cremophor EL and ethanol in Taxol® have rendered patients to severe side effects. Years of extensive research on development of cost effective and safer vehicle for PTX, have failed to provide a promising replacement for Taxol®. MCT was selected as oil owing to its parenteral acceptability, high solubilization capacity and multiple therapeutic benefits in cancer cachexia. PTX precipitation kinetics and reported toxicity profile of Kolliphor HS15 has favored its selection for PTX Self Nanoemulsifying Preconcentrate (PSNP). Presence of 30% free PEG in Kolliphor HS15 (PEG-15-hydroxystearate) restricts its miscibility with MCT, imposing significant challenge in development of MCT rich self nanoemulsifying preconcentrate. Removal of PEG layer from oil-surfactant mixture facilitated the formulation of PSNP with 51% w/w MCT. PSNP exhibited better precipitation kinetic profile, higher PTX loading with negligible hemolysis and histamine release compared to Taxol®. PSNP was bioequivalent to Taxol® , though Vd and MRT was significantly higher than Taxol®. PSNP showed distinctly better profile in inhibiting tumor growth and maintaining body weight with significantly higher % survival. Thus, PSNP can be a safer vehicle with potential clinical benefits. Copyright © 2013 American Scientific Publishers. All rights reserved.