Emerging evidence suggests that minimizing mean perfusion pressure (MPP) deficit during vasopressor therapy for a shock might reduce adverse kidney-related outcomes in the intensive care unit (ICU). Individualizing MPP targets based on patients’ pre-illness basal-MPP was assessed for feasibility and preliminary efficacy in vasopressor-treated patients with shock. At 2 tertiary-level ICUs, 31 patients were enrolled in the ‘before’/observational phase and 31 patients in the ‘after’/intervention phase of this prospective before-and-after trial. The feasibility endpoint was time-weighted average MPP deficiency while on vasopressor therapy. Preliminary efficacy outcomes included new significant AKI, major adverse kidney events (MAKE-14) within 14 days, and 90-day mortality. Patients in the after group had lower MPP-deficit (median 18%, [interquartile range [IQR]: 11–23] vs 4%, [IQR: 2–9], P<0.001) and a lower incidence of new significant AKI (8/31 [26%] vs 1/31 [3%], P=0.01). MAKE-14 (9/31 [29%] vs 4/31 [13%], P=0.12) and 90-day mortality (6/31 [19%] vs 2/31 [6%], P=0.13) between-group differences were not statistically significant. In this preliminary study, an individualized blood pressure target strategy during vasopressor therapy in the ICU was feasible and effective. This strategy should be tested in a larger randomized controlled trial.