OBJECTIVE To investigate the efficacy of EMLA cream and local dry cold application for pain relief before periocular botulinum toxin injection, and to compare these two methods. METHODS In this prospective study, 40 patients underwent bilateral periocular botulinum injections for blepharospasm treatment or wrinkle reduction. Patients were divided into three treatment groups. In the first group (n = 12), cold was applied to the periocular area on one side before injection; the other side served as the control. In the second group (n = 12), topical anesthetic cream (EMLA) was applied to one side and the other side served as the control. In the third group (n = 16), cold was applied to one side and EMLA was applied to the other side. A visual analog scale was used for pain intensity, and patients in the third group were asked which treatment they preferred. RESULTS In the first group, the average pain score on the side where cold was applied was 3.00 +/- 1.70, whereas it was 5.83 +/- 1.40 on the control side (p < 0.001). In the second group, the average pain score on the side receiving EMLA was 3.25 +/- 1.86, and on the control side was 5.83 +/- 1.89 (p < 0.001). In the third group, the average pain score was 3.18 +/- 1.68 for the EMLA side and 3.12 +/- 1.31 for the cooled side (p > 0.05); nine of the 16 patients (56.2%) preferred EMLA. CONCLUSIONS Skin cooling and EMLA applications significantly decrease the pain associated with periocular botulinum toxin injections. Clinically or statistically significant difference in pain scores between the two methods was not noted. Patients had a slight preference for EMLA cream over skin cooling.