Organic halide salt passivation is considered to be an essential strategy to reduce defects in state-of-the-art perovskite solar cells (PSCs). This strategy, however, suffers from the inevitable formation of in-plane favored two-dimensional (2D) perovskite layers with impaired charge transport, especially under thermal conditions, impeding photovoltaic performance and device scale-up. To overcome this limitation, we studied the energy barrier of 2D perovskite formation from ortho-, meta- and para-isomers of (phenylene)di(ethylammonium) iodide (PDEAI2) that were designed for tailored defect passivation. Treatment with the most sterically hindered ortho-isomer not only prevents the formation of surficial 2D perovskite film, even at elevated temperatures, but also maximizes the passivation effect on both shallow- and deep-level defects. The ensuing PSCs achieve an efficiency of 23.9% with long-term operational stability (over 1000 h). Importantly, a record efficiency of 21.4% for the perovskite module with an active area of 26 cm2 was achieved. © 2021, The Author(s).