OBJECTIVES: To evaluate the timing of definitive fixation of tibial plateau fractures relative to fasciotomy closure with regard to alignment and articular reduction. DESIGN: Retrospective case series. SETTING: Four Level I trauma centers. PATIENT SELECTION CRITERIA: Patients with tibial plateau fractures (TPF) with ipsilateral compartment syndrome treated with fasciotomy between 2006 and 2018 met inclusion criteria. Open fractures, patients younger than 18 years, patients with missed or delayed treatment of compartment syndrome, patients with a diagnosis of compartment syndrome after surgical fixation, and patients whose plateau fracture was not treated with open reduction and internal fixation were excluded. Patients were divided into 2 groups depending on the relative timing of fixation to fasciotomy closure: early fixation (EF) was defined as fixation before or at the time of fasciotomy closure, and delayed fixation (DF) was defined as fixation after fasciotomy closure. OUTCOME MEASURES AND COMPARISONS: Radiographic limb alignment (categorized as anatomic alignment (no varus/valgus), ≤ 5 degrees varus/valgus, or >5 degrees varus/valgus) and articular reduction (categorized as anatomic alignment with no residual gap or step-off, <2 mm, 2-5 mm, and >5 mm of articular surface step-off) were compared between early and delayed fixation groups. In addition, superficial and deep infection rates were compared between those in the EF and DF cohorts. Subgroup analysis within the EF cohort was performed to compare baseline characteristics and outcomes between those that received fixation before closure and those that underwent concurrent fixation and closure within one operative episode. RESULTS: A total of 131 patients met inclusion criteria for this study. Sixty-four patients (48.9%) were stratified into the delayed fixation group, and 67 patients (51.1%) were stratified into the early fixation group. In the EF cohort, 57 (85.1%) were male patients with an average age of 45.3 ± 13.6 years and an average body mass index of 31.0 ± 5.9. The DF cohort comprised primarily male patients (44, 68.8%), with an average age of 46.6 ± 13.9 years and an average body mass index of 28.4 ± 7.9. Fracture pattern distribution did not differ significantly between the early and delayed fixation cohorts ( P = 0.754 for Schatzker classification and P = 0.569 for OTA/AO classification). The relative risk of infection for the DF cohort was 2.17 (95% confidence interval, 1.04-4.54) compared with the EF cohort. Patients in the early fixation cohort were significantly more likely to have anatomic articular reduction compared with their delayed fixation counterparts (37.5% vs. 52.2%; P < 0.001). CONCLUSIONS: This study demonstrated higher rates of anatomic articular reduction in patients who underwent fixation of tibial plateau fractures before or at the time of fasciotomy closure for acute compartment syndrome compared with their counterparts who underwent definitive fixation for tibial plateau fracture after fasciotomy closure. The relative risk of overall infection for those who underwent fasciotomy closure after definitive fixation for tibial plateau fracture was 2.17 compared with the cohort that underwent closure before or concomitantly with definitive fixation. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.