The authors investigate which factors were most likely to increase the risk of postoperative urosepsis within 28 days of ureteroscopy (URS) and laser stone fragmentation by analysing the 34 of 562 patients who developed this complication. Stone size, same session bilateral procedure, operative time, the use of an access sheath and being deemed to have residual fragments at follow-up were not associated with increased risk of postoperative sepsis on multivariable analysis. Having a preoperative ureteral stent or nephrostomy was significantly associated with a preoperative positive mid-stream urine (MSU) and postoperative urosepsis. Furthermore, patients with or without a stent who had a positive preoperative MSU were 4.88 times more likely to develop postoperative urosepsis. In conclusion, a positive preoperative MSU was the only factor significantly associated with postoperative urosepsis on multivariable analysis. This paper acts as a welcome reminder to be meticulous with your preoperative urine culture checks. These high-risk patients should be counselled appropriately before surgery, and should be the focus of vigilant postoperative monitoring.