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Introduction: To investigate the efficacy and safety of multi-tract percutaneous nephrolithotomy (PNL) against the benchmark of the single-tract approach.Methods: 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.Results: Multi-tract PNL and single-tract PNL were performed in 37 (9%) and 354 (91%) cases respectively. At baseline, compared to single-tract PNL, multitract PNL cases were characterized by significantly larger stone burden (2.62 vs 0.97 cm 3 , P < .00), lower Hounsfield units (HU) (751 vs 1017 HU, P < .01), a more complex S.T.O.N.E. (size, tract length, obstruction, number of calyces, essence) score (P < .00) and a higher rate of high-risk stone formers (59 vs 19%, P < .00). Analysis of outcome revealed shorter operation time and length of hospital stay for single-tract PNL compared to multi-tract PNL (P < .01). How-