Ti-5Al-5Mo-5V-3Cr-0.5Fe (Ti-5553) has exceptionally good strength-to-density ratio and fracture toughness in the beta-annealed, slow-cooled and aged condition, but exhibits typically challenging, near-beta alloy behavior in machining. In an effort to produce machined components at minimum cost, a study was carried out to relate microstructure and machinability for this alloy. Prior efforts to relate these parameters, in any alloy system, have been few and not particularly revealing. The present effort evaluated machinability for Ti-5553 in various metallurgical states and noted a strong tool life dependence on microstructure. This presentation will cover fundamental aspects of work-piece machinability as a function of microstructure, tool-workpiece interfacial reactions and chip formation mechanisms. Machinability was empirically assessed by quantifying cutting force and tool life characteristics in a controlled end milling operation at constant material removal rates. Microstructures were assessed via standard light and electron microscopy, thermal analysis and x-ray diffraction. The results indicate that tool life can be substantially increased by choosing beneficial microstructures in a given alloy.