The United States, along with other resource-rich countries, leads global health care by advancing medical care through randomized controlled trials (RCTs). While most medical research is conducted in these resource-rich areas, RCTs, including replications of previous trials, are additionally carried out in low- and middle-income countries. On the basis of positive findings from several RCTs conducted in high-income countries, the Antenatal Corticosteroids Trial (ACT) evaluated the effectiveness of antenatal corticosteroids in reducing neonatal mortality in low- and middle-income countries. ACT, however, was undertaken in dramatically different health care infrastructures and did not confirm the results of previous studies. We argue that it is neither clinically appropriate nor ethically acceptable to extrapolate findings from one region to another without accounting for the disparate cultural values, goals of care, and health services infrastructure that impact clinical outcomes.