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 CO2. 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 CO2 uptake and atmospheric CO2 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 CO2 uptake and atmospheric CO2 reduction diverged between the scenarios after the mid-2060s, when atmospheric CO2 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 CO2 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.