Natural ventilation is one of the most important design options for green buildings, which reduces energy use and improves thermal comfort. Computational Fluid Dynamics (CFD) simulations have been used increasingly for natural ventilation design in urban neighborhoods. The accuracy of such simulations relies largely on how the CFD domain is chosen. In the domain, we define the Influence Region as the area where the surrounding buildings must be modeled explicitly to predict the ventilation flow rate accurately. This study presents the early efforts to determine the adequate size of the Influence Region in the CFD domain using a coupled indoor-outdoor CFD simulation, in which the air change rate (ACH) no longer varies noticeably with increasing number of surrounding obstacles. Convergence charts of ACH as a function of an increasing number of surrounding building layers are generated using various urban parameters (e.g., wind condition, aspect ratio, building height relative to surroundings, downstream obstacles, and non-idealized surroundings). Our analysis demonstrated that only including the adjacent layer of surrounding obstacles is not sufficient for predicting correctly the ACH because of the artificial channeling effect between buildings. For both normal and oblique wind directions, three layers of surroundings are required for regular street canyons with an aspect ratio H/W = 1. In the case of wide canyons (H/W = 1/3), two layers of surroundings are needed because there is less flow interference between upstream and downstream obstacles. For the urban configuration, where the target building is significantly taller than nearby structures, the ACH on higher floors does not vary much with increasing amount of surroundings, which significantly reduces the required number of buildings in the Influence Region. In addition, buildings at the side and downstream of the target building can be moderately excluded in the Influence Region as long as the most adjacent downstream layer of obstacles is modeled. A real urban configuration with non-uniform spacing among buildings is evaluated. We showed that the required size of the Influence Region that is derived from uniform building arrays still generally applies to non-idealized landscapes. This study demonstrates the importance of assessing the sensitivity of the selected Influence Region in CFD simulations to reduce unintended modeling errors and computing expense. (C) 2016 Elsevier Ltd. All rights reserved.