Rationale: Spontaneous breathing trials (SBTs) are designed to simulate conditions after extubation, and it is essential to understand the physiologic impact of different methods. Objectives: We conducted a systematic review and pooled measures reflecting patient respiratory effort among studies comparing SBT methods in a meta-analysis. Methods: We searched Medline, Excerpta Medica Database, and Web of Science from inception to January 2016 to identify randomized and nonrandomized clinical trials reporting physiologic measurements of respiratory effort (pressure-time product) or work of breathing during at least two SBT techniques. Secondary outcomes included the rapid shallow breathing index (RSBI), and effort measured before and after extubation. The quality of physiologic measurement and research design was appraised for each study. Outcomes were analyzed using ratio of means. Measurements and Main Results: Among 4,138 citations, 16 studies (n = 239) were included. Compared with T-piece, pressure support ventilation significantly reduced work by 30% (ratio of means [RoM], 0.70; 95% confidence interval [CI], 0.57-0.86), effort by 30% (RoM, 0.70; 95% CI, 0.60-0.82), and RSBI by 20%(RoM, 0.80; 95% CI, 0.75-0.86). Continuous positive airway pressure had significantly lower pressure-time product by 18% (RoM, 0.82; 95% CI, 0.68-0.999) compared with T-piece, and reduced RSBI by 16% (RoM, 0.84; 95% CI, 0.74-0.95). Studies comparing SBTs with the postextubation period demonstrated that pressure support induced significantly lower effort and RSBI; T-piece reduced effort, but not the work, compared with postextubation. Work, effort, and RSBI measured while intubated on the ventilator with continuous positive airway pressure of 0 cm H2O were no different than extubation. Conclusions: Pressure support reduces respiratory effort compared with T-piece. Continuous positive airway pressure of 0 cm H2O and T-piece more accurately reflect the physiologic conditions after extubation.