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Acute kidney failure from light chain cast nephropathy is a serious complication of multiple myeloma. Plasma exchange (PLEX) has been used to remove circulating free light chains (FLCs), but its benefit in the modern treatment era remains uncertain. We performed a retrospective multicenter cohort study using the TriNetX Research Network to identify newly diagnosed multiple myeloma cases presenting between 2014 and 2024 with acute kidney failure and FLC levels > 1500 mg/L. Patients were classified by receipt of PLEX within 7 days. Propensity score matching incorporated demographics, comorbidities, laboratory values, and initial myeloma-directed therapies. The primary outcome was dialysis dependence at 90 days. Secondary outcomes included dialysis dependence at 180 days, mortality, renal recovery (creatinine < 2.0 mg/dL), ICU admission within 7 days, and dialysis-free survival. Among 5454 eligible patients, 251 (4.6%) received PLEX. After matching, 248 patients were included in each group. PLEX was not associated with reduced dialysis dependence at 90 (16.1% vs. 18.1%; OR 0.87, 95% CI 0.54-1.39) or 180 days (18.5% vs. 20.2%; OR 0.90, 95% CI 0.58-1.41). Mortality, ICU admission, and dialysis-free survival were also similar. PLEX was not associated with improved dialysis independence or survival, supporting rapid initiation of effective anti-myeloma therapy.