Using water jets for orthopedic procedures that require bone drilling can be beneficial due to the absence of thermal damage and the always sharp cut. Previously, the influence of the water jet diameter and bone architectural properties on the drilling depth have been determined. To develop water jet instruments that can safely drill in orthopedic surgery, the impact of the two remaining primary factors were determined: the jet time (tjet [s]) and pressure (P [MPa]). To this end, 84 holes were drilled in porcine tali and femora with water jets using Ø 0.4 mm nozzle. tjet was varied between 1, 3 and 5 s and P between 50 and 70 MPa. Drilling depths Lhole (mm), diameters Dhole (mm) and the volume of mineralized bone per unit volume (BV/TV) were determined with microCT scans. A non-linear regression analysis resulted in the predictive equation: Lhole= 0.22 * tjet0.18 * (1.2–BV/TV) * (P–29) (R2=0.904). The established relation between the machine settings and drilling depth allows surgeons to adjust jet time and pressure for the patient׳s BV/TV to drill holes at a predetermined depth. For developers, the relation allows design decisions to be made that influence the dimensions, flexibility and accuracy of water jet instruments. For a pressure of 50 MPa, the potential hole depth spread indicated by the 95% confidence interval is <1.6 mm for all tested jet times. This maximum variance is smaller than the accuracy required for bone debridement treatments (2–4 mm deep), which confirms that water jet drilling can be applied in orthopedic surgery to drill holes in bone with controlled depth.