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To investigate the efficacy and safety of multi-tract percutaneous nephrolithotomy (PNL) against the benchmark of the single-tract approach.A retrospective analysis of 391 consecutive PNL procedures was conducted in our tertiary referral center between April 2016 and March 2020. Clinical outcome parameters such as stone-free rate, operation time, postoperative complications according to Clavien-Dindo, length of hospital stay and time to ipsilateral recurrence resulting in active treatment were assessed.Multi-tract PNL and single-tract PNL were performed in 37 (9%) and 354 (91%) cases respectively. At baseline, compared to single-tract PNL, multi-tract PNL cases were characterized by significantly larger stone burden (2.62 vs 0.97 cmIn this retrospective single-center analysis, a multi-tract PNL has been proved to be an efficient and safe expansion of single-tract PNL for large stone burden and complex kidney stone disease. Future prospective research should focus on the procedure's potential effectiveness in reducing the number of interventions until stone-free status in patients with massive stone disease.