Background: Venipuncture is a common procedure in the emergency department, and in some patients the procedure may cause pain, anxiety, and fear. There are different studies in the literature looking for ways to reduce the pain, either pharmacologically or non-pharmacologically. Most of the studies were done in pediatrics but a few were in adult patients. We conducted this study to determine whether an ice pack application reduces venipuncture pain among emergency department adult patients compared to the conventional way. Methods: We conducted this randomized controlled clinical trial on adult patients in the Security Forces Hospital, Riyadh, Saudi Arabia, from 1 March 2021 to 30 June 2021. Computer randomization was done to randomize subjects to either control or intervention. The 22-gauge needle catheter was inserted in the antecubital fossa in all participants. Results: We included 281 patients aged 18 to 60 years, who were randomized to the control or intervention group. There were 140 patients in the control group and 141 in the intervention group. The mean average pain score in the control group was 2.19 and 1.66 in the intervention group, with a statistically significant difference (p-value: 0.016). Conclusion: The ice pack application reduces venipuncture pain in adult emergency department patients and was associated with a better first attempt success rate.