Background: Previous studies have demonstrated the feasibility of a remifentanil–propofol (RP) mixture use in sedation for medical examinations. However, delivery of an RP mixture by target‑controlled infusion (TCI) for colonoscopy has not been described. Here, we investigate the appropriate proportion of RP mixed regimens, prepared in two different ratios for colonoscopy. Methods: A retrospective study including patients who received a colonoscopy between May 2018 and January 2019 was conducted. Group 1 and Group 2 were, respectively, administered a mixture of RP at concentrations of 2.5 μg/mL-10 mg/mL and 5.0 μg/mL-10 mg/mL by adjusting a TCI pump with Schneider model to keep the Observer’s Assessment of Alertness/Sedation scale between 1 and 2. The primary outcome was to determine the appropriate proportion of RP for the procedure in terms of hemodynamic conditions and adverse events. The secondary endpoints included the total dosage of anesthetics and total times of TCI pump adjustments. Results: A total of 120 patients in Group 1 and 116 patients in Group 2 were eligible for analysis. Several parameters were significantly different between Group 1 and Group 2, with Group 1 having a higher respiratory rate, a lower end‑tidal carbon dioxide pressure, fewer patients with hypotension (mean arterial pressure <60 mmHg; 1 vs. 7, P = 0.033) or apnea with desaturation (peripheral oxygen saturation < 90%; 1 vs. 12, P = 0.001), more propofol consumption (162.4 ± 49.6 mg vs. 130.3 ± 48.8 mg, P < 0.001), less remifentanil consumption (40.6 ± 12.3 μg vs. 65.1 ± 24.4 μg, P < 0.001), and fewer total times of TCI pump adjustment (1 [0–1] vs. 1 [1–2], P < 0.001), as compared to Group 2. Conclusions: In colonoscopy, TCI with an RP mixed regimen prepared in the proportion of 2.5 μg/mL-10 mg/mL with propofol Schneider model target 2.5–3.0 μg/mL provided appropriate hemodynamic conditions, sufficient sedation and analgesia, and less adverse events.