Introduction: Achalasia (AC) is an esophageal motility disorder clinically manifested as dysphagia.Aim: To investigate the effective factors of peroral endoscopic myotomy (POEM) for AC treatment. Material and methods: A total of 182 AC patients treated between August 2019 and September 2020 were enrolled to receive POEM. They were assigned to an effective group (n = 143) and an ineffective group (n = 39). Their clinical data were recorded. The biochemical indices were determined. Results: Compared with the ineffective group, the Eckardt score and incidence of reflux 1 year after the operation were lower in the effective group, and the effective rate 6 months and 1 year after the operation was higher (p < 0.05). Significant differences were observed in drinking history, Eckardt score 1 year after the operation, hemoglobin (Hb), alanine aminotransferease (ALT), white blood cells (WBC), interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) between the two groups (p < 0.05). The Eckardt score 1 year after the operation, WBC, IL-6 and hs-CRP were lower, while the levels of Hb and ALT were higher in the effective group than those in the ineffective group. Multivariate logistic analysis revealed that drinking history, Eckardt score at 1 year after the operation, Hb, ALT, WBC, IL-6, and hs-CRP were independent factors affecting the therapeutic effect of POEM on AC. The results were well fitted by evaluation discrimination and calibration of the nomogram model, with good consistency. Conclusions: POEM is safe, feasible and effective for AC treatment, based on factors such as drinking history, Eckardt score 1 year after the operation, Hb, ALT, WBC, IL-6, and hs-CRP.