In the present study an attempt was made to create micro holes in Ti–6Al–4V titanium alloy by laser machining process. In order to enhance the machinability of the in terms of material removal rate (MRR) and recast layer thickness (RLT), ultrasonic vibration has been associated with the process. A comprehensive experimental study has been carried out to understand interaction effect of ultrasonic assisted laser machining parameters viz. ultrasonic vibration amplitude, laser power, pulse frequency and gas pressure on process quality characteristics. Analysis of variances has been carried out to find which factors has greatest effect on performance measures. Finally an optimization approach based on response surface method was carried out to obtain parameter setting regarding maximum MRR and minimum RLT and taper. Results indicated that the vibration amplitude has greatest effect on improving the MRR and RLT. Results revealed that selection of 40 μm vibration amplitude, 980 W laser power, 1200 Hz modulation frequency and 0.25 MPa gas pressure is an optimal parameter setting yields material removal rate of 2 mm3/min and RLT of 439 μm. The desirability for this parameter setting is 78%.