Introduction: Volumetric modulated arc therapy (VMAT) is an advanced technique used for radiotherapy treatment using different optimization modes. The present study aimed to evaluate Multi-criteria Optimization (MCO) influence on VMAT for Craniospinal Irradiation. Material and Methods: Fifteen CSI patients treated with 23.4 Gy/13 fractions followed by a boost dose of 6-MV flattening filter-free beams were chosen for this study. Conventional VMAT (c-VMAT) plans were generated for Elekta Versa HD™ linear accelerator. Keeping all other parameters constant, c-VMAT plans combined with MCO (MCO-VMAT) were created for comparison. We compared homogeneity index (HI), conformity index (CI), planning target volume (PTV) dose coverage (D98%), organ at risk (OAR) dose, normal tissue integral dose (NTID), volume receiving ≥ 5 Gy and ≥ 10 Gy by normal tissue, delivery time (DT), monitor units (MUs), and calculation time (CT). Results: Our findings demonstrated that HI and CI improved slightly in MCO-VMAT, in comparison with c-VMAT (P>0.05). No significant dose difference was observed in D98% for PTV and volume receiving the dose of ≥ 5 Gy, ≥ 10 Gy, and NTID (P>0.05). A slight increase was found in maximum dose to PTV in VMAT-MCO, compared to c-VMAT (P>0.05). The mean dose, max dose, and dose received by OAR were significantly lower in VMAT-MCO as compared to c-VMAT (p 0.05). Conclusion: The MCO-VMAT can be used for CSI, without compromising target coverage, reduced OAR dose by accepting a slight increase of MUs, delivery and calculation time as compare to c-VMAT.