Neopentyl glycol diester as a biolubricant was successfully synthesized in a solvent free system with fatty acid and neopentyl glycol using an immobilized lipase as a biocatalyst. Immobilization was carried out with a liquid enzyme, Eversa transform 2.0 (from Thermomyces lanuginose) and Lewatit VP OC 1600, a macroporous hydrophobic resin, as a carrier. The effects of enzyme loading and temperature as a function of reaction times were explored under no vacuum condition. The maximum yield of ca. 63% was achieved at optimal temperature of 50 oC and enzyme loading of 5% (based on the total weight of the substrate) under no vacuum. However, the yield of neopentyl glycol diester increased markedly up to 97%, even though vacuum as low as 200 torr was applied. No significant differences in the yield of neopentyl glycol diester between constant vacuum condition, and combination of vacuum and no vacuum condition were observed. This combination method employed in this study is a novel strategy for synthesis of neopentyl glycol diester.