Introduction: Ureteroscopic lithotripsy has become the first choice for the treatment of middle and lower ureteral stones, but it still has a certain rate of surgical failure. Here we aimed to determine the factors that may affect the success rate of holmium laser ureterolithotripsy (HLU) and provide the basis and guidance for its future use. Aim: To evaluate the risk factors for HLU failure. Material and methods: The clinical data of 385 patients undergoing holmium laser ureterolithotripsy from 2009 to 2012 were retrospectively reviewed to analyze the impact of gender, age, stone side, stone size, stone location, stone number, degree of hydronephrosis, stone impaction, previous extracorporeal shock lithotripsy (ESWL), and associated urinary tract infection (UTI) on the success or failure of surgery. Results: Surgical success was achieved in 338 (87.8%) patients versus surgical failure in 47 (12.2%) patients. Univariate analysis revealed that the degree of hydronephrosis (p = 0.024), stone impaction (p = 0.003), stone location (p = 0.012), and previous ESWL (p = 0.037) were risk factors for surgical failure. Multivariate logistic regression revealed that stone impaction (odds ratio (OR) = 2.66; p = 0.018) and stone location (OR = 2.11; p = 0.013) were significantly associated with surgical failure. Since some cases of ureterostenosis developed postoperatively, we continued follow-up. The patients had the stent for a year and underwent regular follow-up checks until 5 years. No cases of ureterostenosis recurred. Conclusions: Ureteroscopic lithotripsy is a safe procedure with few complications. Stone impaction and proximal location are the risk factors for its failure.