Retrospective comparative study. This study compared outcomes for patients managed with a lateral approach to interbody fusion [lateral (LLIF) or oblique (OLIF)] versus a posterior (PLIF) or transforaminal interbody fusion (TLIF) for treatment of adjacent segment disease (ASD) above or below a prior lumbar fusion construct. No study has compared outcomes of lateral approaches to more traditional posterior approaches for the treatment of ASD. Retrospective review was performed of patients who underwent single-level lateral or posterior approaches for lumbar interbody fusion for symptomatic ASD between January 2010 and December 2021. Exclusion criteria included skeletal immaturity (age below 18y old) and surgery indication for malignancy or infection. Patient demographics, medical comorbidities, operative details, postoperative complications, and revision surgery profiles were collected for all patients. Standard descriptive statistics were used to summarize data. Comparative statistical analyses were performed using Statistical Package for the Social Sciences (Version 28.0.1.0; Chicago, IL). A total of 152 patients (65±10y) were included in the study with a mean duration of follow-up of 1.6±1.4 years. The cohort included 123 PLIF/TLIF (81%), 18 LLIF (12%), 11 OLIF (7%). TLIF/PLIF experienced greater mean operative time (210±62min vs. 184±80 OLIF/105±64 LLIF, P<0.001) and estimated blood loss (414±254mL vs. 49±29 OLIF/36±33 LLIF, P<0.001). No significant difference in rate of postoperative complications. Postoperative radicular pain was significantly greater in OLIF (7, 64%) and LLIF (7, 39%) compared with PLIF/TLIF (16, 13%), P<0.001. No statistically significant difference in health care utilization was noted between the groups. Lateral fusions to treat ASD demonstrated no significantly different risk of complication compared with posterior approaches. Our study demonstrated significantly increased operative time and estimated blood loss for the posterior approach and an increased risk of radicular pain from manipulation/retraction of psoas following lateral approaches. Level III.