Objective To investigate the effects of holmium laser lithotripsy (HLL) and pneumatic lithotripsy (PL) under ureteroscope on the stress response and lithotripsy effectiveness in elderly patients with upper ureteral calculi (UUC). Methods Totally 100 elderly patients with UUC hospitalized in our department from June 2016 to June 2018 were recruited in this study. They were equally and randomly divided into HLL group and PL group. The effects of operation, lithotripsy, postoperative serum levels of cortisol (Cor) and adrenocorticotropic hormone (ACTH), and incidences of complications were compared between the 2 groups. SPSS statistics 22.0 was used to perform the statistical analysis. Chi-square test or Student′s t test was employed for comparison between the groups. Results The HLL group had significantly less volume of intraoperative bleeding [(60.97±7.02) vs (83.25±9.24)ml], shorter operative time [(66.43±6.81) vs (85.43±8.72)min], shorter lithotripsy time [(31.88±3.55) vs (40.45±4.22)min], less length of hospital stay [(6.42±1.07) vs (7.65±1.11)d], and lower serum levels of Cor [(387.11±40.12) vs (437.13±45.43) ng/ml] and ACTH [(14.02±1.54) vs (15.71±1.68)pmol/L] after operation when compared with the PL group (all P<0.01). What′s more, the success rate of single lithotripsy [100%(50/50) vs 88%(44/50), P=0.012] and stone removal rate [96%(48/50) vs 84%(42/50), P＝0.046] were obviously higher, while the incidences of complications were notably lower [6%(3/50) vs 20%(10/50), P=0.037] in the HLL group than the PL group. Conclusion HLL under ureteroscope effectively reduces the surgical trauma, complications and stress response in the elderly patients with UUC, with good lithotripsy effect. It is worthy of further clinical promotion.