Purpose: This study aimed to determine the impact of an intervention using voice recording of family members on pain, anxiety, and agitation in patients undergoing weaning from mechanical ventilation. Methods: A randomized control pre-post experimental design was implemented to 53 participants, with 27 and 26 participants in the experimental and control groups, respectively. A 70-second voice recording of a family member, repeated three times at 10-minute intervals was used as an intervention for the experimental group. Meanwhile, participants in the control group used headset for 30 minutes. Structured instruments were utilized to measure pain, anxiety, agitation, and the weaning process. Wilcoxon Signed Ranks test and the Mann-Whitney U test, or χ2 test, were used for data analysis. Results: The experimental group exhibited significant decrease in pain (Z = - 3.53, p < .001), anxiety (t = 5.45, p < .001), and agitation (Z = - 2.99, p = .003) scores compared with those of the control group. However, there was no significant difference between groups in the weaning process’ simplification (χ2 = 0.63, p = .727). Conclusion: Intervention using family members’ voice recording effectively reduces pain, anxiety, and agitation in patients undergoing weaning from mechanical ventilation. This can be actively utilized to provide a more comfortable process for patients.