Since patients often experience pain and unpleasantness during a colonoscopy, the present study aimed to evaluate the efficacy and safety of sublingually administered fentanyl tablets for pain treatment. Furthermore, since the use of intravenous drugs significantly increases colonoscopy costs, sublingual tablets could be a cost-effective alternative to intravenous sedation. We conducted a prospective placebo-controlled randomized study of 158 patients to evaluate the analgesic effect of a 100 µg dose of sublingual fentanyl administered before a colonoscopy. Pain, sedation, nausea, and satisfaction were assessed during the colonoscopy by the patients as well as the endoscopists and nurses. Respiratory rate and peripheral arteriolar oxygen saturation were monitored throughout the procedure. There were no differences between the fentanyl and placebo groups in any of the measured variables. The median pain intensity values, as measured using a numerical rating scale, were 4.5 in the fentanyl group and 5 in the placebo group. The sedation and oxygen saturation levels and the respiratory rate did not differ between the groups. The majority of the colonoscopies were completed.Our results indicate that a 100 µg dose of sublingual fentanyl is not beneficial compared to the placebo in the treatment of procedural pain during a colonoscopy.