Background: Combinations of infero-temporal and either supero-nasal (‘inferior–superior’) or medial percaruncular (‘inferior–medial’) injections are popular double-injection techniques for establishing peribulbar block analgesia. This study compared the efficacy of these two techniques in achieving ocular and lid akinesia. Methods: One hundred patients were randomized to receive inferior–superior or inferior–medial injections in a study in which injectate, injectate volumes, 5-min ocular akinesia scoring (0–8), lid scoring (0–2) and supplemental injection protocols were standardized. The numbers of supplemental injections required at each observation period and the total volume of injectate required to produce ocular and lid akinesia were compared. Results: The two test groups were demographically similar. The inferior–medial combination achieved greater ocular akinesia than the inferior–superior combination 5 min after the initial injections (mean score ± standard deviation of 1.74 ± 1.86 vs. 2.66 ± 2.39; P < 0.05), with a reduced requirement for supplementary injections (3 vs. 23 supplementary injections; P < 0.025). The inferior–superior technique achieved greater lid akinesia at 5 min than the inferior–medial technique (mean score ± standard deviation of 0.7 ± 0.9 vs. 0.3 ± 0.58; P < 0.005). A medial subconjunctival hemorrhage occurred in one patient in the inferior–medial group. Conclusion: Compared with the inferior–superior technique, the inferior–medial combination achieved more rapid ocular akinesia with less need for supplementation, but induced less efficient lid akinesia and had a propensity to cause iatrogenic subconjunctival hemorrhage. The latter complication is considered by our surgeons to be a contraindication to the inferior–medial technique in patients undergoing trabeculectomy.