Marine cloud brightening (MCB) is a geoengineering proposal to cool atmospheric temperatures and reduce climate change impacts. As large-scale approaches to stabilize global mean temperatures pose governance challenges, regional interventions may be more attractive near term. Here we investigate the efficacy of regional MCB in the North Pacific to mitigate extreme heat in the Western United States. Under present-day conditions, we find MCB in the remote mid-latitudes or proximate subtropics reduces the relative risk of dangerous summer heat exposure by 55% and 16%, respectively. However, the same interventions under mid-century warming minimally reduce or even increase heat stress in the Western United States and across the world. This loss of efficacy may arise from a state-dependent response of the Atlantic Meridional Overturning Circulation to both anthropogenic warming and regional MCB. Our result demonstrates a risk in assuming that interventions effective under certain conditions will remain effective as the climate continues to change. Regional marine cloud brightening (MCB) has been proposed as a form of geoengineering. Here the authors show that a regional MCB aiming to reduce warming in the Western United States under today’s conditions would be less efficient under warmer conditions and would exaggerate warming in other regions.