Cincinnati Children's Hospital Medical Center (CCHMC) relocated the pediatric, cardiac, and neonatal intensive care units (PICU, CICU and NICU) to a newly constructed critical care building (CCB) in November 2021. Simulation and onboarding sessions were implemented before the relocation, aimed at mitigating latent safety threats. To evaluate the impact of ICU relocation to the CCHMC CCB on patient safety as measured by the quantity, rate, severity score, and category of safety reports. This retrospective, cross-sectional, observational study compared safety reports filed in a 90-day period before and following the CCB relocation. The primary outcome was pre- and postrelocation safety report rates per 100 patient-days. Secondary outcomes included safety report severity, category, and rate of hospital acquired conditions (HACs). Total safety report incidence increased by 16% across all ICUs postrelocation with no difference in post- versus prerelocation odds ratio between ICUs. Three isolated instances of special cause variation were found, one in NICU and two in CICU. No special cause variation was found in the PICU. There were no statistical differences in assigned safety report severity pre- to postrelocation for all ICUs, and only lab specimen/test related safety reports showed a statistically significant increase postrelocation. Overall rates of HACs were low, with six occurring prerelocation and eight postrelocation. All three ICUs were relocated to the new CCB with minimal changes in the incidence, severity, or category of safety reports filed, suggesting staff training and preparations ahead of the relocation mitigated latent safety threats.