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Rationale: Research supports the use of screening protocols to identify patients who are candidates for weaning from mechanical ventilation, and the use of spontaneous breathing trials (SBTs) to predict ability to breathe spontaneously. However, once daily screening is poorly aligned with 24-hour continuous care in the intensive care unit (ICU) environment and the most effective SBT technique is not known. The optimal strategy to liberate our sickest patients from ventilators remains to be determined. Objectives: To assess our ability to recruit critically ill adults and adhere to the screening and SBT protocols. Methods: We propose a pilot, factorial design, randomized trial comparing once-daily versus at least twice daily screening and pressure support (PS) ± positive end-expiratory pressure (PEEP) (inspiratory ± expiratory support) or T-piece (no support) as the SBT technique in critically ill adults who are invasively ventilated for at least 24 hours in 11 North American ICUs. Respiratory Therapists (RTs) will screen all enrolled patients between 06:00 and 08:00 hours daily to identify SBT candidates. Patients in the at least twice daily screening arms will also be screened between 13:00 and 15:00 hours; additional screening will be permitted at clinician’s discretion. Once a screening assessment is passed, an SBT will be conducted with the assigned technique. Outcomes: The study will be considered feasible if at least 1 to 2 patients per ICU per month are recruited and if the screening and SBT protocols are adhered to >80% of the time. Relevance: The availability of RTs in ICUs presents an important opportunity to screen patients more frequently, conduct more frequent SBTs, and reduce the duration of invasive ventilation and ICU stay. FAST Trial Registration: Clinical Trials.gov NCT02399267.