Background Peroral endoscopic myotomy (POEM) is a novel treatment for achalasia with excellent outcomes. But the predictor for treatment failure is not well defined. This study was aimed to prospectively investigate the factors for predicting failed POEM. Methods From June 2011 to May 2015, a total of 115 achalasia patients treated by POEM were included for the retrospective cohort study from Nanfang Hospital and the First People's Hospital of Yunnan Province. Patients were followed up with Eckardt score, high-resolution manometry and endoscope. POEM failure was defined as primary failure (Eckardt score failed to decrease to 3 or below) and recurrences (decrease of Eckardt score to 3 or below, then rise to more than 3) during one-year follow-up. Univariate and multivariate Cox regression analyses were performed to assess the predictive factor. For the associated factor, receiver operating characteristic curve (ROC) was utilized to determine the cutoff value of the predicting factor. Results The failure rate of POEM after 1 year was 7.0% (8/115), including 5 primary failure cases and 3 recurrences. Multivariate analysis showed higher pre-treatment Eckardt score was the single independent factor associated with POEM failure [9.5 (6-12) vs. 7 (2-12), odds ratio (OR) 2.24, 95 confidence interval (95% CI) 1.39-3.93, p = 0.001]. The cutoff value (Eckardt score C9) had 87.5 sensitivity (95% CI 47.3-99.7%) and 73.8% specificity (95% CI 64.4-81.9%) for predicting failed POEM. Conclusions Pre-treatment Eckardt score could be a predictive factor for failed POEM. Eckardt score C9 was associated with high sensitivity and specificity for predicting POEM failure.