<h3>BACKGROUND CONTEXT</h3> The role of fusion in degenerative spondylolisthesis (DS) is controversial. The Clinical and Radiographic Degenerative Spondylolisthesis (CARDS) and Degenerative Spondylolisthesis Instability Classification (DSIC) systems were developed to assist surgeons in surgical technique selection based on individual patient characteristics. These systems have not been clinically validated. Additionally, it is unclear if baseline radiographic findings such as slip magnitude, angular and translational motion, and facet effusion are useful in guiding technique selection. <h3>PURPOSE</h3> The purpose of this study was to determine if outcomes vary with different surgical techniques across the CARDS and DSIC categories and with certain baseline radiographic findings. <h3>STUDY DESIGN/SETTING</h3> Prospective cohort study performed at one Swiss and one American spine center. <h3>PATIENT SAMPLE</h3> A total of 508 degenerative spondylolisthesis patients undergoing surgical treatment. <h3>OUTCOME MEASURES</h3> Core Outcomes Measure Index (COMI) at 3 months and 12 months postoperatively. <h3>METHODS</h3> DS patients undergoing surgery were enrolled at two institutions in Switzerland and the United States, and classified according to the CARDS and DSIC systems. MRIs were analyzed for Pfirrmann grade, disc height loss, presence of Schmorl's nodes, Modic changes, central and foraminal stenosis severity, magnitude of listhesis, magnitude of facet joint effusion, and facet joint angle. Dynamic radiographs were analyzed for magnitude of listhesis, disc height, bony apposition, kyphosis, translation, and intervertebral rotation. The Core Outcomes Measure Index (COMI) was completed at baseline, 3 months, and 12 months postoperatively. Due to small numbers in some subgroup analyses, patients treated with decompression alone or decompression with uninstrumented fusion were combined for analysis (uninstrumented group) as were patients treated with decompression and posterolateral instrumented fusion or decompression with posterolateral and interbody instrumented fusion (instrumented group). Unadjusted analyses and mixed effect models compared COMI scores between the two surgery technique groups (uninstrumented vs instrumented), stratified by CARDS and DSIC category and radiographic characteristics over time. Reoperation rates were also compared between the surgery technique groups stratified by CARDS and DSIC category. <h3>RESULTS</h3> A total of 508 patients were enrolled in the study, 460 had sufficient data to be classified according to CARDS, 459 could be classified according to DSIC, and 490 had radiographic images available for analysis. Seven percent were classified as CARDS A, 28% as CARDS B, 48% as CARDS C, and 17% as CARDS D (CARDS A most "stable", CARDS D least "stable"). 2% were classified as DSIC 1, 80% as DSIC 2, and 17% as DSIC 3 (DSIC 1 most "stable, DSIC 3 least "stable"). One hundred thrity-three patients (26%) underwent decompression alone, 30 (6%) underwent decompression and uninstrumented fusion, 42 (8%) underwent decompression and posterolateral instrumented fusion, and 303 (60%) underwent decompression with posterolateral and interbody instrumented fusion. Patients in the least "stable" categories tended to be less likely to be treated with an uninstrumented technique (CARDS D 19% and DSIC 3 21% vs 32% for the other categories, p=0.10 for CARDS, p=0.02 for DSIC). There were no significant differences in 3- or 12-month COMI scores between surgical technique groups stratified by CARDS or DSIC category in the unadjusted or adjusted analyses. In the unadjusted analyses, there was a trend toward less improvement in 12-month COMI change score in the CARDS D patients in the uninstrumented group compared to the instrumented group (-3.01 vs -3.88, p=0.10). Reoperation rates were not significantly different between the surgical technique groups stratified by CARDS and DSIC category. There were no significant differences between the surgical technique groups across the different radiographic characteristics. There was a nonsignificant trend toward more improvement in the instrumented group in patients with severe foraminal stenosis and larger facet joint effusions. <h3>CONCLUSIONS</h3> In general, outcomes for uninstrumented and instrumented surgical techniques were similar across the DSIC and CARDS categories. There was a trend toward less improvement in the CARDS D patients treated with uninstrumented techniques, suggesting that in patients with kyphosis (the defining feature of the CARDS D category) better outcomes may be associated with instrumentation. Baseline radiographic findings were generally not associated with different outcomes across the surgical technique groups. The major limitation of this study was the low numbers in the CARDS D (n=15) and DSIC 3 (n=17) uninstrumented groups, likely due to surgeons choosing to avoid uninstrumented techniques in these patients. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.