Cellulose nanofibrils (CNF) have gained increased attention since the last fifteen years and can now be produced at high solid content in an energetically efficient way using twin-screw extrusion (TSE). In this study, screw profile was optimized using a simulation software in order to produce high quality CNF in one pass through the TSE, instead of several passes in other studies, decreasing the energy consumption, improving the productivity and hence making the industrialization of such process more probable. An optimized profile was designed using the software according to previous studies and enzymatic cellulose pulp was experimentally nanofibrillated. Produced CNF were characterized using several techniques such as optical microscopy, mechanical properties, turbidity, nanosized fraction or quality index. The optimized screw profile contains six blocks of kneading disks with left-handed staggering and imparts high levels of shear, strain and energy in the first pass. CNF were successfully produced in a single pass with equivalent quality than CNF produced in at least 4 passes using a classic profile, without changing the energy consumption. Produced CNF present high transparency and a Young's modulus around 13 GPa.