Context: Posttraumatic ankle instability (PAI) is likely a multifactorial condition that results from mechanical and sensorimotor insufficiencies. Recent research has focused on identifying specific factors that make the greatest contribution to the development of PAI, thereby helping elucidate the underlying causes of PAI. However, a limited understanding of this complex pathology still exists because of conflicting results. Using more homogenous cohorts of participants with PAI could help facilitate the identification of and treatment for specific sources of self-reported disability, perceived instability, and recurrent ankle sprains in patients with PAI. Objective: The primary aim for the current study was to determine whether sensorimotor and mechanical variables differ among homogenous groups of participants with PAI established based on the presence of self-reported instability, repeated episodes of “giving-way,” and recurrent ankle sprains. The secondary aim was to identify specific mechanical and sensorimotor factors that would most strongly associate with the major clinical symptoms. Design: A single-blinded, case control. Setting: Research laboratory. Patients or Other Participants: A total 87 participants volunteered for this current study and were allocated to the five participant groups (recurrent ankle sprains with perceive instability [RAS-PI], recurrent ankle sprainers [RAS], functional ankle instability [FAI], ankle sprain copers, and healthy controls). Twenty-four participants with RAS-PI (14M, 10F; 22.54+4.05yrs; 171.56+8.83cm; 76.38+15.06kg), 11 participants with RAS (5M, 6F; 22.27+4.98yrs; 169.68+9.62cm; 74.35+22.55kg), 12 participants with FAI (4M, 8F; 20.83+1.59yrs; 165.76+6.54cm; 65.67+11.77kg), and 16 ankle sprain copers (6M, 10F; 21.06+3.45yrs; 167.76+11.57cm; 73.00+17.92kg) were compared to 24 healthy control participants (9M, 15F; 21.54+3.30yrs; 166.82 +7.82cm; 67.28+13.49kg). Methods: Measures of sensorimotor and mechanical outcomes were conducted. Main Outcomes: Sensorimotor outcome measures included 1) spinal reflex excitability assessed with the Hmax: Mmax ratio calculated from the maximal Hoffman (H)-reflex and muscle-response, 2) the amount of efferent nerve impulses traveling in the alpha motoneuron assessed with the V-wave and maximal muscle –response (V: Mmax ratio), 3) corticospinal excitability assessed using the transcranial magnetic stimulation for active motor threshold (AMT) and cortical silent period (CSP), 4) static postural control assessed with center of pressure velocity (COPV) and time-to-boundary (TTB) measures, 5) dynamic postural control assessed with the star excursion balance test in the anterior reach direction (SEBT-A), and movement variability during gait assessed with approximate entropy (ApEn). Mechanical outcome measures included 1) ankle joint laxity measured as displacements in the anterior-posterior directions (mm) and rotation in the eversion-inversion directions (degrees) using ankle arthrometer, 2) weight bearing ankle dorsiflexion range of motion (DF-ROM) using the weight bearing lunge test (WBLT) (cm), and 3) non-weight bearing DF-ROM using a bubble inclinometer (degrees). ¬Statistical Analyses: Aim 1: A separate independent samples Kruskal-Wallis test was used to examine the difference for each outcome variable that was not normally distributed. For sensorimotor outcome variables that were found to be normally distributed, one-way ANOVAs were performed to examine differences between groups. For each mechanical outcome variable, a separate ANCOVA was used to examine difference between groups (covariate=sex). Fisher’s LSD post-hoc or a Mann-Whitney U test was used in the event of statistical significance. Cohen’s d effect sizes with associated 95% confidence intervals (CI) were calculated using the pooled standard deviations. Aim 2: The discriminant functional analysis (DFA) was used to investigate the contribution of each significant factor on the determination of group membership. An A priori alpha level was set at P < 0.05 using SPSS 21.0 (SPSS, Inc. Chicago, IL.) for Windows for all statistical tests. Results: Aim 1: Spinal reflex excitability (Hmax: Mmax ratio) was diminished in participants with RAS-PI and FAI compared to those with RAS, ankle sprain copers and healthy controls participants (F4, 86=2.643, P =0.039). The V: Mmax ratio did not differ among the groups (H4 = 9.069, P = 0.059). However, moderate effect sizes were found for V: Mmax ratio between the RAS-PI and ankle sprain coper groups (d=-0.79). For static postural control, the RAS-PI group demonstrated higher COPV in the anteroposterior (AP) (H4 = 14.574, P = 0.006) and in the mediolateral (ML) (H4 = 10.542, P = 0.032) directions compared to the control and coper groups. For the TTB measures of static postural control, no differences were observed among the groups (p > 0.05). However, effect size analysis revealed that the RAS-PI group had lower mean TTB-ML (d = -0.77) and SD of TTB-ML (d = -0.82) compared to the control group. No significant results were observed for other sensorimotor and mechanical outcome measures (P > 0.05). Aim 2: Neural excitability and static postural control measures correctly classified 45.83% of participants with RAS-PI (Wilk’s ¿ = 0.578, ¿224 = 44.194, P = 0.007). Conclusion: Decreased spinal reflex excitability of the soleus and impaired static postural control were observed in participants with PAI. Neural excitability and static postural control measures were shown to be the most influential factors of the selected outcome measures in this study to classify group memberships. The results may lead to therapeutic interventions that target decreased spinal reflex excitability and static postural control to improve clinical outcomes for PAI.