Monooctanoin is used clinically for dissolution of common bile duct cholesterol gallstones. A number of factors influencing the dissolution rate of cholesterol monohydrate in this solvent were investigated. Water increased cholesterol dissolution rate in a manner inconsistent with previous solubility measurements. Dissolution rate increased approximately 50% in the presence of 10 to 15% water in monooctanoin. Further studies on viscosity, the effect of polymers and temperature showed that the solvent viscosity had a dominating influence on dissolution rate. This was thought to be caused by the interaction of cholesterol with the solvent in the dissolving surface layer which caused a decrease in the diffusion coefficient (and dissolution rate) of cholesterol. Reducing viscosity and increasing temperature were identified as possible approaches for increasing cholesterol gallstone dissolution rate in monooctanoin.