Retrospective review. To compare perioperative and postoperative clinical outcomes between minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and lateral lumbar interbody fusion (LLIF) in patients presenting with predominant back pain. Two popular techniques utilized for lumbar arthrodesis are MIS-TLIF and LLIF. Both techniques have reported high fusion rates and suitable postoperative clinical outcomes. Scarce literature exists, however, comparing these 2 common fusion techniques in a subset population of patients presenting with predominant back pain preoperatively. A retrospective review of lumbar procedures performed between November 2005 and December 2021 was conducted using a prospectively maintained single-surgeon database. Inclusion criteria were set as primary, elective, single, or multilevel MIS-TLIF or LLIF procedures for degenerative spinal pathology in patients with predominant preoperative back pain [visual analog scale (VAS) back pain preoperative score > VAS leg preoperative score]. Patients undergoing a revision procedure, single-level procedure at L5-S1, or surgery indicated for infectious, malignant, or traumatic etiologies were excluded. In addition, patients with VAS leg preoperative scores ≥ to VAS back preoperative scores were excluded. Patient demographics, perioperative characteristics, postoperative complications, and patient-reported outcome measures (PROMs) were collected. PROMs included VAS for back and leg pain, Oswestry Disability Index (ODI), and Short Form-12 (SF-12) Item Survey Mental (MCS) and Physical (PCS) Composite Scores with all values collected at the preoperative, 6-week, 12-week, 6-month, 1-year, and 2-year follow-up time point. Patients were grouped into 2 cohorts, depending on whether a patient underwent a MIS-TLIF or LLIF. Demographic and perioperative characteristics were compared between groups using χ2 and Student t test for categorical and continuous variables, respectively. Mean PROM scores were compared between cohorts at each time point utilizing an unpaired Student t test. Postoperative improvement from preoperative baseline within each cohort was assessed with paired samples t test. Achievement of minimum clinical important difference (MCID) was determined by comparing ΔPROM scores to previously established threshold values. MCID achievement rates were compared between groups with χ2 analysis. Statistical significance was noted as a P value <0.05. Eligible study cohort included 153 patients, split into 106 patients in the MIS-TLIF cohort and 47 patients in the LLIF cohort. The mean age was 55.9 years, the majority (57.5%) of patients were males, the mean body mass index was 30.8kg/m2, and the majority of the included cohort were nondiabetic and nonhypertensive. No significant demographic differences were noted between cohorts. The MIS-TLIF cohort had a significantly greater proportion of patients with preoperative spinal pathology of recurrent herniated nucleus pulposus, whereas a significantly greater proportion of patients in the LLIF cohort demonstrated isthmic spondylolisthesis (P < 0.046, all). No significant differences were noted between cohorts for operative duration, estimated blood loss, 1-year rate of arthrodesis, postoperative length of stay, postoperative VAS pain scores on postoperative day 0 or 1, and postoperative narcotic consumption on postoperative day 0 or 1. Patients in the LLIF cohort showed greater rates of postoperative ileus (4.3% vs 0.0%). No other significant differences were noted between cohorts for postoperative complications. Between cohorts, preoperative PROM scores did not significantly differ. The following significant postoperative mean PROM scores were demonstrated: VAS back at 12 weeks and ODI at 12 weeks with both mean scores favoring the LLIF cohort. The MIS-TLIF cohort reported significant improvement from preoperative baseline to the 2-year time point for all PROMs collected at all individual postoperative time points except SF-12 MCS at 6 weeks (P < 0.0, all). LLIF cohort reported significant improvement from preoperative baseline to the 1-year time point for all PROMs collected at all individual postoperative time points except for ODI at 6 weeks, 1 year, and 2 years, SF-12 MCS at 6 weeks and 2 years, and SF-12 PCS at 2 years(P < 0.042, all). The majority of patients in both cohorts achieved overall MCID for VAS back, VAS leg, ODI, and SF-12 PCS. A significantly greater proportion of patients in the LLIF cohort achieved MCID for SF-12 PCS at 12 weeks (94.4% vs 61.1%; P < 0.008). Patients with predominant back pain undergoing MIS-TLIF or LLIF for degenerative spinal pathology demonstrated similar 2-year mean clinical outcomes for physical function, disability, leg pain, and back pain. At the 12-week time point, mean outcome scores for back pain and disability favored the lateral approach with concurrent higher rates of MCID achievement for physical function at that time point.