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The objective of the study is to identify and evaluate possible factors that influence the ability to run before and after single event multi-level surgery (SEMLS). Young patients (6–25 years) with spastic cerebral palsy (GMFCSI-II) were retrospectively included. Type and number of surgical procedures, time for recovery and 3D gait analysis variables were analyzed with respect to the ability to run. In total, 98 patients (38 females; 60 males) who received SEMLS (12 years, SD 3.4) were included and compared to a control group of 71 conservatively treated patients. Of 60 runners pre-surgery, 17 (28%) lost the ability, while gained in 8 of 38 (21%) non-runners. The number of surgical procedures was a significant predictor and those who lost their ability to run had significantly more (mean = 5.9, SD = 1.7), compared to the patients who gained the ability (mean = 3.5, SD = 0.9). Further, pre-surgical function (e.g., gait speed) was significantly different (p < 0.001). Pre-surgical function and the number of surgical procedures seem to play an important role for the gain or loss of the ability to run after surgery. Caution is warranted in patients with lower pre-surgical function and the ability to run, as they seem at a higher risk to lose the ability. [ABSTRACT FROM AUTHOR]