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Clinical practice guidelines, care pathways, and protocols are designed to support evidence-based practices for clinicians; however, their adoption remains a challenge. We set out to investigate why clinicians deviate from the “Wake Up and Breathe” protocol, an evidence-based guideline for liberating patients from mechanical ventilation in the intensive care unit (ICU). We conducted over 40 hours of direct observations of live clinical workflows, 17 interviews with frontline care providers, and 4 co-design workshops at three different medical intensive care units. Our findings indicate that unlike prior literature suggests, disagreement with the protocol is not a substantial barrier to adoption. Instead, the uncertainty surrounding the application of the protocol for individual patients leads clinicians to deprioritize adoption in favor of tasks where they have high certainty. Reflecting on these insights, we identify opportunities for technical systems to help clinicians in effectively executing the protocol and discuss future directions for HCI research to support the integration of protocols into clinical practice in complex, team-based healthcare settings.