Background/Objectives: To compare postoperative infectious complication rates after ureteroscopy (URS) in patients with anatomical anomalies of the urinary tract and neurogenic bladder to those in patients without these conditions, and to analyze associated risk factors, urine culture profiles, and stone composition in these special populations. Methods: This retrospective cohort study included patients undergoing URS at a single tertiary referral center. Patients were stratified into three groups: anatomical anomalies of the urinary tract (n = 23), neurogenic bladder (n = 30), and controls (n = 297). Demographic data, perioperative details, preoperative urine culture results, stone composition, and postoperative complications were collected and compared. Univariable analyses and chi-square or Kruskal–Wallis tests were used as appropriate. Results: Patients with anatomical anomalies of the urinary tract and neurogenic bladder had significantly higher rates of postoperative infectious complications compared to controls (30.4% and 33.3% vs. 4.0%; p < 0.001). Preoperative urine cultures were more frequently positive in these groups, with Escherichia coli, Enterococcus faecalis, and Pseudomonas aeruginosa being the most common pathogens. Stone analysis revealed a higher proportion of struvite and mixed calcium phosphate stones in the anatomical anomalies of the urinary tract and neurogenic bladder groups compared to controls, who predominantly formed calcium oxalate stones (75%). Conclusions: Patients with anatomical anomalies of the urinary tract or neurogenic bladder are at higher risk of postoperative infectious complications following URS, likely due to more frequent colonization and anatomical or functional urinary tract abnormalities. These findings underscore the importance of tailored perioperative management, including targeted antimicrobial strategies and careful surgical planning, to mitigate risks in these high-risk populations.