Abstract Background Pregnancy-related acute kidney injury (PrAKI) is an uncommon but serious complication associated with adverse maternal and neonatal outcomes, with limited data in high-resource settings. Methods We conducted a retrospective cohort study of 29 586 deliveries at Mayo Clinic hospitals between 2017 and 2022. PrAKI was defined using Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. Maternal characteristics, nephrotoxin exposure, clinical interventions, and neonatal outcomes were compared between patients with and without PrAKI. Results PrAKI occurred in 341 patients (1.15%). Compared with controls, PrAKI was associated with higher rates of chronic hypertension (28.7% vs 5.2%), cesarean delivery (68.5% vs 35.1%), intensive care unit (ICU) admission (59.1% vs 6.2%), and nephrotoxin exposure (58.7% vs 31.6%) (all P < .0001). Dialysis was required in 7.1% of patients with PrAKI, with 1.17% remaining dependent at discharge and 0.88% at 30 and 90 days; no control patients required dialysis. Neonates of mothers with PrAKI had higher rates of prematurity and neonatal ICU (NICU) admission (48.7% vs 9.8%; P < .0001). Maternal mortality was rare. Conclusions PrAKI is a marker of severe maternal illness and is associated with adverse maternal and neonatal outcomes. Although most patients recover kidney function, a subset develop persistent dysfunction. Early identification, cautious use of nephrotoxic medications, and structured postpartum follow-up are essential.