Abstract: Objective To investigate the therapeutic effect of botulinum toxin A on middle-aged and elderly patients with postherpetic neuralgia (PHN) as well as anxiety and depression. Methods A total of 100 PHN patients who were admitted to the Affiliated Hospital of Xuzhou Medical University from December 2019 to January 2021 were enrolled. According to the random number table method, they were divided into two groups (n=50): a botulinum toxin A group (group BTX-A) and a control group (group C). Both groups were compared for their numeric rating scale (NRS) scores, patient health questionnaire depression scale (PHQ-9) scores, and generalized anxiety disorder scale (GAD-7) scores before treatment (T0), one week after treatment (T1), four weeks after treatment (T2), and 12 weeks after treatment (T3). After 12 weeks of treatment, the improvement of the overall sleep quality scores (SQS) in both groups was assessed. The doses of daily oral gabapentin and opioids, and the incidence of adverse reactions were recorded. Results Compared with those at T0, both groups presented decreases in the scores of NRS, GAD-7 and PHQ-9 at T1 to T3 after treatment. The scores of NRS, GAD-7 and PHQ-9 in group BTX-A were significantly improved compared with those in group C at each time points after treatment (P<0.05). After 12 weeks of treatment, group BTX-A showed significantly improved SQS scores compared with group C (P<0.05). There was no difference in the doses of oral gabapentin and the use of opioids (P>0.05). No statistical difference was found in the incidence of adverse reactions between the two groups (P>0.05). Conclusions Botulinum toxin A can relieve pain in middle-aged and elderly patients with PHN, and improve anxiety and depression to a certain extent.