PurposeTo compare the efficacy of two botulinum toxin (BoNT) injection methods, pretarsal (PT) combined with preseptal (PS) injection (PT-PS) and conventional PT injection, in the treatment of benign essential blepharospasm (BEB). DesignProspective nonrandomized clinical trial. MethodsFrom January 2023 to April 2024, 95 BoNT injections into orbicularis oculi were performed in 45 BEB patients, including 52 PT-PS injections s and 43 PT injections. Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BSDI) were used to assess motor symptoms. The efficacy of two injection methods for BEB was compared in terms of latency to response (LTR), latency to the peak response (LPR), duration of peak response (DPR), duration of response (DOR), satisfaction degree, and possible complications. ResultsBoth injection methods significantly improved JRS and BSDI scores in patients with BEB. However, PT-PS injections showed a shorter LTR [(4.00(3.00,6.00) vs 5.00(4.00,7.00) days, p=0.024] and LPR [23.50(16.00,26.00) vs 26.00(20.00,30.00) days, p=0.040], a longer DPR [88.00(80.50,104.75) vs 75.00(65.00,92.00) days, p=0.003] and DOR [135.00(118.50,153.75) vs 121.00(107.00,135.00) days, p=0.003] than PT injections. Patients with PT-PS injections were more satisfied than those with PT injections [9.50(8.50,10.00) vs 8.00(7.50,9.00), p<0.001], and around 2/3 of patients were more willing to receive the combined injection method later. Among patients receiving PT-PS injections, only one case experienced ptosis, and there were no significant differences in other complications such as lacrimation, dry eyes, and blurred vision between the two injection methods. ConclusionsPT-PS injections of BoNT showed more advantages in the treatment of BEB than PT injections in terms of both their efficacy and patients’ satisfactions.