Abstract Ocean Alkalinity Enhancement (OAE) refers to the addition of alkaline material to the surface ocean, which shifts carbonate chemistry towards more oceanic uptake of atmospheric CO 2 . This study compares global OAE with regionally focused deployment in subduction regions of the Southern Ocean, Northwest Atlantic, and Norwegian-Barents Sea. We conducted ensemble simulations using an emissions-driven Earth System Model (ESM) under high- (SSP3-7.0) and low-emissions (SSP1-2.6) scenarios. By 2100, subduction region OAE was nearly as efficient (SSP3-7.0: 0.71±0.03, SSP1-2.6: 0.60±0.04) as global deployments (SSP3-7.0: 0.73±0.01, SSP1-2.6: 0.64±0.03). However, the ESM simulations did not reproduce the efficient vertical carbon transport seen in a previous ocean-only study, as strong internal variability and climate feedbacks to OAE hampered deep ocean carbon storage. The excess ocean CO 2 uptake and atmospheric CO 2 reduction were scenario-dependent (15-19% and 22-41% lower under SSP1-2.6 compared to SSP3-7.0, respectively). The pathways of excess ocean CO 2 uptake and atmospheric CO 2 reduction diverged between the scenarios after the mid-2060s, when atmospheric CO 2 peaked and then declined under SSP1-2.6, with a substantially larger relative land carbon loss in SSP1-2.6 than in SSP3-7.0 for regional OAE deployment. Furthermore, the emissions-driven ensemble simulations showed that climate feedbacks introduced substantial uncertainty in early decades of regional OAE efficiency, posing challenges for near-term Monitoring, Reporting, and Verification. Reviewing our and previous model experiments revealed a strong linear relationship between added alkalinity and oceanic CO 2 uptake and atmospheric reduction, highlighting that first-order effects of OAE on carbonate chemistry are well understood and consistently represented, while the effects of carbon and climate feedbacks (13-20%) and scenario sensitivity are smaller but non-negligible. Overall, our study shows that subduction regions can be a viable option for OAE; however, their efficiency is limited by these feedbacks and scenario sensitivity, which must be accounted for in future regional OAE interventions.