Objective To assess the effect of esketamine on the wake‑up test in orthopedic surgery for adolescent scoliosis. Methods A total of 80 patients who were treated with selective orthopedic surgery for adolescent scoliosis were recruited. Using the random number table method, patients were divided into the esketamine group (SK group, n=40) and the control group (C group, n=40). When anesthesia induction was performed, 0.25 mg/kg esketamine was additionally administrated in patients of the SK group, followed by intravenous infusion of 0.25 mg·kg−1·h−1 esketamine; while those in the C group were given the same volume of normal saline. Anesthesia maintenance in both groups was performed by intravenous infusion of propofol and remifentanil. Propofol was given at the initial dosage of 5 mg·kg−1·h−1, the infusion rate of which was adjusted to maintain the bispectral index (BIS) of 45−55. Remifentanil was given at the initial dosage of 0.25 μg·kg−1·min−1, and subsequently increased or reduced stepwise by 0.05 μg·kg−1·min−1 according to hemodynamic changes. The wake‑up time was recorded and the wake‑up quality was assessed. Ramsay sedation scores and Riker agitation scores at wake‑up were recorded. This article recorded the mean arterial pressure (MAP) and heart rate 10 min before awakening (T0), at the time of successful awakening (T1), and after falling asleep again (T2), the MAP and heart rate changes of T0−T1 and T1−T2 (ΔMAP, ΔHR) were calculated. The anesthesia time before wake‑up and during the whole surgery, dose of propofol and remifentanil, blood loss, and the use of vasoactive drugs were also recorded. In addition, length of stay in the post‑anesthesia care unit (PACU), time of extubation, Visual Analog Scale (VAS) scores, Ramsay sedation scores, Riker agitation scores, and the incidence of adverse events like nausea, vomiting, and nightmares after surgery were recorded. Results Baseline characteristics, anesthesia time before wake‑up and during the whole surgery, dose of propofol, blood loss, use of vasoactive drugs, length of stay in PACU, time of extubation, and incidence of adverse events in the SK group and C group were comparable (P>0.05). Compared with C group, the quality of wake‑up test in SK group showed an increase in the proportion of grade I and a decrease in the proportion of grade Ⅱ and Ⅲ, and the patients in SK group presented shorter wake⁃up time, higher Ramsay sedation scores, lower Riker agitation scores, and less dose of remifentanil before wake⁃up and during the whole surgery (P<0.05). ΔMAP and ΔHR (T0−T1, T1−T2) during wake‑up in the SK group were significantly smaller than those in the C group (P<0.05). In addition, patients in the SK group were graded significantly higher Ramsay sedation scores, lower Riker agitation, and lower VAS scores after postoperative recovery (all P<0.05). Conclusions Anesthesia induction by esketamine at 0.25 mg/kg and continuous intravenous infusion of 0.25 mg·kg−1·h−1 esketamine effectively enhances the intraoperative wake‑up quality, shortens the wake‑up time, stabilizes hemodynamics during wake‑up, and reduces the intraoperative dose of remifentanil, which is favorable to improve the safety and quality of anesthesia.