Abstract Nowadays, Ti6Al4V alloy is widely used to fabricate miniaturized prostheses, orthopedic and dental implants. Surface quality is an essential aspect of the implant parts owing to its effect on service life, which could be achieved through a proper selection of precise micromachining parameters. In this research, the mechanical micromachining of Ti6Al4V alloy has been performed, and optimized process parameters are considered for analysis. Surface roughness (R a ) of the machined microchannels, cutting force in the feed direction (F y ), cross-feed direction (F x ), and vibration on the top surface plate along the spindle axis (a z ) have been taken as the response variables and were analyzed. The tests were accomplished at various rotational speed (N), feed per tooth (f z ), axial depth of cut (a p ), and cutter diameter (D) as machining parameters, each at three levels. The significant factors and their levels are identified using analysis of variance (ANOVA) and S/N ratios of response plot. According to the GRA test, N : 15000 rpm, fz : 0.2 µm/tooth, ap : 30 µm, and D : 200 µm are optimal parameters setting for better machinability of Ti6Al4V. ANOVA results indicated that feed rate is the most influential factor for lower cutting forces, surface roughness, and workpiece vibration. Fast Fourier transform (FFT) analysis depicts the stiffness of different micro end-mills significantly affect the machining performance like vibration amplitude during the micro-milling of Ti6Al4V alloy.