Urosepsis is a serious potential complication of ureteroscopic procedures for stone disease, yet the risk factors for this complication are not well characterized. The purpose of this systematic review with meta-analysis was to identify potential risk factors for urosepsis after ureteroscopy (URS) for stone disease. We performed systematic searches of Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies reporting at least one prospectively defined risk factor for urosepsis after URS. Studies that only reported rates of isolated fever, urinary tract infection (UTI), or pooled infectious complications were excluded. The risk factors evaluated in this review were age, sex, body mass index, diabetes mellitus, ischemic heart disease, recent UTI, pyuria, hydronephrosis, stone history, stone size, preoperative stent placement, preoperative positive urine culture, and procedure time. A random effects meta-analysis model with inverse variance weighting was used where the statistic of interest was the odds ratio for dichotomous variables and the mean difference for continuous outcomes. In 13 studies (5 prospective) with 5597 patients, the pooled incidence of postoperative urosepsis was 5.0% (95% confidence interval: 2.4-8.2). Six risk factors were statistically associated with increased postoperative urosepsis risk-preoperative stent placement (odds ratio = 3.94, p < 0.001, 6 studies), positive preoperative urine culture (odds ratio = 3.56, p < 0.001, 6 studies), ischemic heart disease (odds ratio = 2.49, p = 0.002, 2 studies), older age (mean difference = 2.7 years, p = 0.002, 6 studies), longer procedure time (mean difference = 9 minutes, p = 0.02, 1 study), and diabetes mellitus (odds ratio = 2.04, p = 0.04, 6 studies). Current evidence suggests that among patients undergoing URS for treatment of stone disease, the risk of postoperative urosepsis was 5.0%. Older age, diabetes mellitus, ischemic heart disease, preoperative stent placement, a positive urine culture, and longer procedure time were associated with increased postoperative urosepsis risk. These results will assist urologists with preoperative risk stratification before ureteroscopic procedures.