Background Mismanagement of remifentanil leads to severe side effects such as opioid-induced tolerance and hyperalgesia. Recently studies revealed an alternative withdrawal method to limit these side effects. A gradual withdrawal of remifentanil seems to be associated with less pain. The hypothesis of this double-blinded, randomized controlled trial was that a gradual withdrawal of remifentanil would be associated with less immediate post-operative pain compared to after an abrupt discontinuation of remifentanil in patients who underwent thyroid surgery. Methods This double-blinded, randomized controlled trial was conducted in a tertiary level hospital in Brussels (Belgium) from April until August 2017. 34 patients undergoing thyroid surgery were randomized and 29 patients completed the study. After randomization, patients undergoing thyroid surgery were allocated to two groups: one with an abrupt discontinuation of remifentanil after surgery and one with a gradual withdrawal of remifentanil after surgery. The primary outcome was the initial post-operative demand of analgesic medication. Results Gradual withdrawal of remifentanil was associated with a delayed initial post-operative demand of analgesic medication ( P = 0.006). The first morphine bolus was given after 76.3 +/− 89.0 min in the group with a gradual withdrawal of remifentanil versus after 9.0 +/− 13.5 min in the group with an abrupt discontinuation of remifentanil. However, overall morphine consumption, numeric rating scale scores, Ramsay Sedation Scale scores, and quality of recovery scores (QoR-40) were similar in both groups ( P > 0.05). Conclusion Though overall morphine consumption, numeric rating scale scores, Ramsay Sedation Scale scores, and quality of recovery scores (QoR-40) are not altered, a gradual withdrawal of remifentanil after thyroid surgery is safe and associated with a delayed initial post-operative demand of analgesic drugs. The withdrawal process does, however, require vigilance and training. Trial registration Clinicaltrials.gov NCT03110653 (PI: Luc Barvais; date of registration: 03/31/2017).