<h3>BACKGROUND CONTEXT</h3> The institution of single positioning throughout a combined approach to adult spinal surgery has many theorized benefits, including minimizing surgical measures like operative time and estimated blood loss that are highly correlated with higher rates of postoperative complications. However, prone lateral positioning has yet to be correlated to other important outcomes, including radiographic realignment and patient-reported outcomes. <h3>PURPOSE</h3> To investigate the surgical and postoperative outcomes of the prone lateral single-position approach to adult spinal deformity surgery. <h3>STUDY DESIGN/SETTING</h3> Retrospective review of a single-center database. <h3>PATIENT SAMPLE</h3> This study included 524 MIS patients. <h3>OUTCOME MEASURES</h3> Perioperative outcomes [EBL, LOS, op-time, lvls fused], intraoperative and postoperative complication rates, patient-reported outcomes. <h3>METHODS</h3> Operative spine fusion patients available baseline (BL) and up to two-year (2Y) data from a single-center database were isolated. Patients were stratified into two groups based on undergoing a prone lateral single-position combined approach, Prone Lateral (PL) vs MIS Non-Prone Lateral (NPL). Descriptive analyses and means comparison tests identified differences in baseline (BL) demographics, surgical details, radiographic parameters, rates of intraoperative and postoperative complications, and follow-up patient-reported outcomes up to 2 years. <h3>RESULTS</h3> A total of 233 patients (average age: 56.1±11.4 years, average BMI: 30.6±6.6 kg/m2, 54% of the cohort was male, CCI: 1.2±1.9) met inclusion criteria and underwent surgery (operative time: 320±152, EBL: 374±400 mL, levels fused: 2.4±1.2, LOS: 4.6±3.7 days). Regarding approach, 3 (1.3%) underwent lateral approach, 86 (38.6%) posterior, and 144 (60.1%) were combined. BL radiographic parameters: PI: 56.2±11.2, lumbar lordosis (LL): 53.0±12.9, PI-LL: 3.3±13.1, PT: 18.2±8.4, sacral slope (SS): 38.3±8.6. There were 103 same-day combined (lateral and posterior) procedures included in the cohort, with 22 of those being performed in the prone-lateral single position. When examining baseline demographics, the PL patients had mean age of 65.0±10.7, BMI of 28.3±4.7, CCI: 2.1±3.7, with 59% being male. Patients undergoing a prone lateral procedure had an average of 2.4±1.1 levels fused, EBL of 192±152 mLs, operative time of 200±103 minutes, while undergoing decompressions in 64% of procedures and osteotomies in 10%. Patients in the PL group were significantly older compared to non-PL patients (p <.001) with a lower BMI (p=.030) and higher CCI (p=.013). Patients undergoing PL procedures had lower EBL and operative time compared to non-PL patients (both p-value <.001), along with less osteotomies performed (10% vs. 43%, p=.002). Although, PL patients had a similar number of levels fused, they had a higher average LIV (L5 vs S1, p=.003) and UIV (L2 vs L3, p=.004) compared to the rest of the cohort. There were no radiographic differences preoperatively or postoperatively, although 50% of PL patients improved to aligned in PI-based sacral slope (GAP Relative Pelvic Version). PL patients suffered significantly less pulmonary (0% vs 4%, p=.019) and GI complications (0% vs 3%, p=.039), but endured higher rates of urinary retention (14% vs 5%, p=.032). This translated to a shorter length of stay (3.3 days vs 4.7, p=.004) for PL patients, with discharge to a rehab facility less often after leaving the hospital (0% vs 13%, p <.001). When examining patient-reported outcomes within one year after surgery, PL patients had greater improvement in NRS-Back (-6.0 vs -3.3, p=.031) and trending toward greater improvement in NRS-Leg (-4.6 vs -3.6, p=.132). <h3>CONCLUSIONS</h3> Patients undergoing prone lateral single-position procedures in this single-center database displayed less invasive procedures with similar degree of correction, endured lower rates of certain complications correlating to going home earlier and more often. These perioperative outcomes correlated to greater improvement of back pain following spinal corrective surgery. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.