OBJECTIVE: Optimal surgical management of spinal metastatic disease remains controversial. Skip and diffuse spinal lesions, patient frailty, and the need for timely adjuvant chemoradiation complicate surgical decision-making. Minimally invasive percutaneous pedicle screw fixation (MIPSF) is an attractive concept that can confer stability and allow early postoperative mobilization. To date, outcomes of the MIPSF technique remain under-investigated. METHODS: A single-center retrospective review of patients undergoing percutaneous instrumentation for multilevel spinal metastatic disease between January 2012 and October 2020 was performed. Twenty-four patients were identified, and their primary tumor diagnoses, modified Tokuhashi scores, Spine Instability Neoplastic Scores, neurologic functions, pain scores, and procedure types were noted. Of these patients, 17 underwent fixation of 6 or more levels (L-MIPSF), whereas 7 underwent fixation of <6 levels (S-MIPSF). All patients had screw-and-rod constructs placed percutaneously using bi-planar fluoroscopy guidance. Patients undergoing corpectomy, multilevel laminectomies, or open posterior instrumentation were excluded. RESULTS: Improvement in pain and neurological function was noted in nearly all patients who underwent MIPSF. Average skin incision-to-closing time was 130 minutes, and standard deviation of 55 minutes. Likewise, the average estimated operative blood loss was 402 mL, and standard deviation of 388 mL. Only one patient required hardware revision due to proximal loss of fixation. Two patients required mini-open decompression procedures due to tumor recurrence at different levels than the index pathology. CONCLUSIONS: Multilevel minimally invasive spinal fixation is feasible in patients with diffuse spinal metastasis. The percutaneous nature of the technique minimizes dissection, blood loss, and operative times. Early outcomes of MIPSF are promising and demonstrate utility in avoiding multiple subsequent procedures in a cohort of deconditioned patients.