Introduction: The goal was to determine risk factors for Clavien-Dindo (CD) grade ≥2 complications, with special focus on early postoperative systemic inflammatory response syndrome (SIRS), for flexible ureteroscopy (fURS). Materials and Methods: A retrospective monocentric statistical analysis relating to 32 factors was performed with the χ2 test, Mann-Whitney U tests, and multivariate logistic regression. Results: In total, 416 consecutive fURS performed between September 2013 and June 2017 were analyzed; 283 (68.03%) of these were for stone surgery and 133 (31.97%) for diagnostic purposes. In 43 cases (10.34%), CD ≥2 occurred; 31 cases (72.09%) of these were SIRS. On multivariate logistic regression, positive preoperative urine culture and steep pyelographic and CT-based infundibulopelvic angle (IPA) have been confirmed as independent risk factors for both CD ≥2 and SIRS. Greater maximal median stone diameter and female gender were significantly associated only with a higher CD ≥2 prevalence, but not with SIRS. The influence of ureteral access sheath (UAS) on CD ≥ 2 or SIRS occurrence could not be confirmed on multivariate analysis. Perioperative antibiotic prophylaxis for patients with negative urine culture showed no difference regarding SIRS prevalence. Conclusion: Steep CT-based IPA can be considered as a new radiologic predictor of complicated postoperative course and SIRS. The role of UAS as well as indications for perioperative antibiotic prophylaxis should be determined in prospective studies.