In mid-2012, the Abdus Salam International Centre for Theoretical Physics (ICTP) released version 4.3 of the Regional Climate Model (RegCM4.3). This version includes a new surface scheme, the Common Land Model (CLM); a new planetary boundary layer (PBL) scheme, the University of Washington PBL (UW-PBL); and new convection schemes including Tiedtke, and Mixed1 and Mixed2—with Grell (MIT) over the land and MIT (Grell) over the ocean for Mixed1 (Mixed2). These implementations suggest the necessity of an evaluation study to determine the best configuration of RegCM4.3 for simulating the climate of South America (SA). The main motivation is to come up with the best configurations of RegCM4.3 over the SA domain for use in the Coordinated Regional Downscaling Experiment (CORDEX) project. We analyzed 7 simulations for the period 1990-2000. The control simulation used the Biosphere-Atmosphere Transfer Scheme (BATS), Holtslag for the PBL and Mixed1 for cumulus convection. In the other simulations we changed these schemes using the new RegCM4.3 options. The evaluation of the simulations was carried out in 3 groups: (1) sensitivity to convection (Mixed1, MIT and Tiedtke), (2) sensitivity to the PBL (Holtslag and UW-PBL) and (3) sensitivity to surface processes (BATS and CLM). Considering all of SA, the results show that precipitation is better simulated with the schemes of the control simulation, while for air temperature, better results were obtained using the MIT cumulus scheme together with the CLM scheme. In summary, we recommend 2 configurations for the CORDEX project over SA: (1) the schemes used in the control simulation and (2) the MIT scheme for cumulus convection, Holtslag for the PBL, and CLM for surface interaction processes.