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Aims: To investigate the efficacy of pre‐emptive remifentanil in alleviating pain during tracheal suctioning in patients under mechanical ventilation. Background: Goal‐directed sedation is recommended for patients under mechanical ventilation by the current guidelines. Whether goal‐directed sedation can prevent pain during tracheal suctioning in these patients is unknown. Design: This was a two‐centre, randomized, crossover, single‐blind trial conducted between August and October 2019. Methods: Patients under mechanical ventilation received low‐dose remifentanil, high‐dose remifentanil or placebo prior to each tracheal suctioning in a random order. The primary outcomes were evaluated using the critical‐care pain observation tool and Richmond agitation–sedation scale after tracheal suctioning. Adverse events were also documented. Results: A total of 39 patients who underwent 117 tracheal suctions were enrolled. After the tracheal suction, changes in the critical‐care pain observation tool and Richmond agitation–sedation scale scores were significantly lower in the low‐dose and high‐dose groups than in the placebo group (P < 0.001). A non‐significant increase in the absence of spontaneous breathing was observed in the high‐dose group compared to that in the placebo group. Conclusion: A pre‐emptive remifentanil bolus of 0.5 μg/kg can mitigate the pain associated with tracheal suctioning. SUMMARY STATEMENT: What is already known about this topic? Pre‐emptive analgesia is recommended by several guidelines to alleviate the pain associated with invasive and potentially painful procedures in ICU patients.Goal‐directed sedation can shorten the length of hospital stay and is recommended for patients in the ICU by several clinical practice guidelines.Literature regarding whether goal‐directed sedation management or pre‐emptive remifentanil can prevent the pain associated with tracheal suctioning in patients under mechanical ventilation is scarce. What this paper adds? A pre‐emptive remifentanil bolus of 0.5 μg/kg can mitigate the pain associated with tracheal suctioning. The implications of this paper: Normal opioid doses administered for goal‐directed sedation management might be insufficient to prevent the pain associated with tracheal suctioningPre‐emptive analgesia can alleviate the pain without increasing the risk of opioid‐related adverse events in ICU patients under mechanical ventilation. [ABSTRACT FROM AUTHOR]