This is an update of a review last published in Issue 5, 2010, of The Cochrane Library. Reducing weaning time is desirable in minimizing potential complications from mechanical ventilation. Standardized weaning protocols are purported to reduce time spent on mechanical ventilation. However, evidence supporting their use in clinical practice is inconsistent. The first objective of this review was to compare the total duration of mechanical ventilation of critically ill adults who were weaned using protocols versus usual (non-protocolized) practice.The second objective was to ascertain differences between protocolized and non-protocolized weaning in outcomes measuring weaning duration, harm (adverse events) and resource use (intensive care unit (ICU) and hospital length of stay, cost).The third objective was to explore, using subgroup analyses, variations in outcomes by type of ICU, type of protocol and approach to delivering the protocol (professional-led or computer-driven). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2014), MEDLINE (1950 to January 2014), EMBASE (1988 to January 2014), CINAHL (1937 to January 2014), LILACS (1982 to January 2014),  ISI Web of Science and ISI Conference Proceedings (1970 to February 2014), and reference lists of articles. We did not apply language restrictions. The original search was performed in January 2010 and updated in January 2014. We included randomized controlled trials (RCTs) and quasi-RCTs of protocolized weaning versus non-protocolized weaning from mechanical ventilation in critically ill adults. Two authors independently assessed trial quality and extracted data. We performed a priori subgroup and sensitivity analyses. We contacted study authors for additional information. We included 17 trials (with 2434 patients) in this updated review. The original review included 11 trials. The total geometric mean duration of mechanical ventilation in the protocolized weaning group was on average reduced by 26% compared with the usual care group (N = 14 trials, 95% confidence interval (CI) 13% to 37%, P = 0.0002). Reductions were most likely to occur in medical, surgical and mixed ICUs, but not in neurosurgical ICUs. Weaning duration was reduced by 70% (N = 8 trials, 95% CI 27% to 88%, P = 0.009); and ICU length of stay by 11% (N = 9 trials, 95% CI 3% to 19%, P = 0.01). There was significant heterogeneity among studies for total duration of mechanical ventilation (I(2) = 67%, P < 0.0001) and weaning duration (I(2) = 97%, P < 0.00001), which could not be explained by subgroup analyses based on type of unit or type of approach. There is evidence of reduced duration of mechanical ventilation, weaning duration and ICU length of stay with use of standardized weaning protocols. Reductions are most likely to occur in medical, surgical and mixed ICUs, but not in neurosurgical ICUs. However, significant heterogeneity among studies indicates caution in generalizing results. Some study authors suggest that organizational context may influence outcomes, however these factors were not considered in all included studies and could not be evaluated. Future trials should consider an evaluation of the process of intervention delivery to distinguish between intervention and implementation effects. There is an important need for further development and research in the neurosurgical population.