© 2016 Wolters Kluwer Health, Inc. All rights reserved. Background: Rib fractures are identified in 10% of all injury victims and are associated with significant morbidity (33%) and mortality (12%). Significant progress has been made in the management of rib fractures over the past few decades, including operative reduction and internal fixation (rib ORIF); however, the subset of patients that would benefit most from this procedure remains ill-defined. The aim of this project was to develop evidence-based recommendations. Methods: Population, intervention, comparison, and outcome (PICO) questions were formulated for patients with and without flail chest. Outcomes of interest included mortality, duration of mechanical ventilation (DMV), hospital and intensive care unit (ICU) length of stay (LOS), incidence of pneumonia, need for tracheostomy, and pain control. A systematic review and meta-analysis of currently available evidence was performed per the Grading of Recommendations Assessment, Development, and Evaluation methodology. Results: Twenty-two studies were identified and analyzed. These included 986 patients with flail chest, of whom 334 underwent rib ORIF. Rib ORIF afforded lower mortality; shorter DMV, hospital LOS, and ICU LOS; and lower incidence of pneumonia and need for tracheostomy. The data quality was deemed very low, with only three prospective randomized trials available. Analyses for pain in patients with flail chest and all outcomes in patients with nonflail chest were not feasible due to inadequate data. Conclusion: In adult patients with flail chest, we conditionally recommend rib ORIF to decrease mortality; shorten DMV, hospital LOS, and ICU LOS; and decrease incidence of pneumonia and need for tracheostomy. We cannot offer a recommendation for pain control, or any of the outcomes in patients with nonflail chest with currently available data. Level of Evidence: Systematic review/meta-analysis, level III.