ImportanceAsymptomatic blood pressure (BP) elevations in the hospital are commonly treated with as-needed BP medications, including recurring as-needed and 1-time administration. Veterans represent a population at risk of ischemic events from rapid lowering of BP, but the impact of as-needed BP medication use in this population is unknown.ObjectiveTo assess the risks of acute kidney injury (AKI) and other outcomes from as-needed BP medication administration in a hospitalized veteran cohort.Design, Setting, and ParticipantsThis retrospective cohort study using target trial emulation and propensity score matching included adult veterans, who were hospitalized 3 or more days in Veterans Administration hospitals between October 1, 2015, and September 30, 2020. Participants must have been hospitalized on a non–intensive care unit medical or surgical floor, must not have undergone surgery, and must have received at least 1 scheduled BP medication in the first 24 hours of admission. Participants also must have had at least 1 systolic BP more than 140 mm Hg during hospitalization. Data in this study were analyzed from April 2023 to August 2024.Main Outcomes and MeasuresThe primary outcome was time to first AKI occurrence during hospitalization. Secondary outcomes included greater than 25% reduction in systolic BP within 3 hours of as-needed BP medication administration and the composite outcome of myocardial infarction, stroke, or death during hospitalization.ResultsOf the 133 760 veterans eligible for analysis (mean [SD] age, 71.2 [11.6] years), 96% were male. The mean (SD) baseline estimated glomerular filtration rate was 75.7 (22.7) mL/min/1.73m2. A total of 28 526 patients (21%) received as-needed BP medication. As-needed BP medication use was associated with an increased AKI risk (adjusted hazard ratio, 1.23 [95% CI, 1.18-1.29]) compared to nonusers. Subgroup analyses showed higher AKI risk with intravenous as-needed BP medication use (compared to oral or combined oral and intravenous routes). Secondary analyses indicated as-needed BP medication users had a 1.5-fold greater risk of rapid BP reduction (95% CI, 1.39-1.62) and 1.69-fold higher rate of the composite outcome (95% CI, 1.49-1.92) compared to nonusers.Conclusions and RelevanceThe results of this retrospective cohort study showed that as-needed BP medication use among veterans is associated with increased AKI risk. The risks and benefits of this type of BP medication use would best be determined through a prospective trial, and these data suggest that there is the necessary equipoise to conduct such a trial.