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Objectives: Peroral endoscopic myotomy (POEM) is an effective treatment for esophageal motility disorders including achalasia and its variants. However, some surgeons have encountered challenging cases. This study aimed to develop a risk‐scoring system to predict challenging cases of POEM. Methods: Consecutive patients who underwent POEM between April 2015 and March 2020 at our hospital were included in this single‐center retrospective study. Challenging cases of POEM were defined as patients with any of the following: (i) procedure time ≥90 min; (ii) mucosal perforation; (iii) pneumothorax; and (iv) major bleeding. A risk‐scoring system for predicting challenging cases was developed based on multivariate logistic regression and internal validation was performed using the bootstrap method. Clinical usefulness was evaluated using a decision curve analysis. Results: Of the 467 patients, 59 (12.6%) had challenging POEM. A risk‐scoring system consisted of four variables: duration of symptoms ≥5 years (assigned score, 1 point), antithrombotics use (1 point), manometric diagnosis of achalasia variants (2 points), and dilation grade 3 (2 points). Our scoring system showed satisfactory discrimination (area under the receiver operating characteristic curve, 0.69; 95% confidence interval [CI] 0.61–0.77) and calibration (slope, 0.99; 95% CI 0.65–1.35). The decision curve analysis demonstrated its clinical usefulness. Conclusions: We established a risk‐scoring system to predict challenging cases of POEM. This scoring system may aid the selection of patients who require treatment from experienced surgeons. [ABSTRACT FROM AUTHOR]