Study Design. Retrospective cohort. Objective. To investigate and establish minimum clinically important differences (MCID) for Patient Health Questionnaire-9 (PHQ-9) among patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). Summary of Background. Spine surgery is linked to postoperative improvements in anxiety, depression, and mental health. These improvements have been documented using patientreported outcome measures such as PHQ-9. Few studies evaluated the clinical significance of PHQ-9 for lumbar spine surgery. Methods. Patients who underwent single-level, primary MIS TLIF from 2015 to 2017 were retrospectively reviewed in a prospective database. Patients with incomplete preoperative and 2-year postoperative PHQ-9 surveys were excluded. Demographic and perioperative characteristics were recorded. PHQ-9, 12-Item Short Form (SF-12), and Veterans RAND 12-Item Health Survey (VR-12) Mental Component Summary (MCS) were collected at preoperative, 6-week, 12-week, 6-month, 1-year, and 2-year intervals. MCID was calculated using anchor and distribution-based methods. SF-12 served as an anchor. MCID was assessed using mean change methodology, four receiver operating characteristic curve assessments, and standard error measurement. Cutoff values were selected from receiver operating characteristic curve analysis. MCID achievement rates for all patient-reported outcome measures were calculated. Results. A total of 139 patients met inclusion criteria, with a mean age of 55 years and 39% females. The most common spinal pathology was radiculopathy (92%). MCID analysis revealed the following ranges of values: 2.0 to 4.8 (PHQ-9), 6.7 to 12.1 (SF-12 MCS), and 7.5 to 15.9 (VR-12 MCS). Final MCID thresholds were 3.0 (PHQ-9), 9.1 (SF-12 MCS), and 8.1 (VR-12 MCS). MCID achievement at 2-years for PHQ-9, SF-12 MCS, and VR-12 MCS was 89.2%, 85.6%, and 84.9% respectively. Conclusion. Our 2-year postoperative MCID analysis is the first mental health calculation from an MIS TLIF cohort. We report a 2-year MCID value for PHQ-9 of 3.0 (2.0-4.8). MCID values for mental health instruments are important for determining overall success of lumbar spine surgery.