INTRODUCTION: We conducted a systematic review and meta-analysis to assess the available literature regarding the postoperative effects of anti-reflux anastomosis and direct anastomosis in orthotopic ileal neobladder (ONB). METHODS: We searched PubMed, Embase, and the Cochrane Library in October 2021. We included 11 studies of patients with bladder cancer who underwent radical cystectomy and ONB as urinary diversion. Outcomes evaluated in this review were ureteroenteric anastomotic stricture (UEAS), vesicoureteral reflux, renal function (RFn) impairment, and pyelonephritis. All data were analyzed using Review Manager 5.4.4 and subgroup analyses were applied. RESULTS: A total of 11 studies were eligible for meta-analysis. The synthetic data suggested that anti-reflux anastomosis and direct anastomosis were comparable in terms of RFn impairment (odds ratio (OR) = 1.69; 95% confidence interval (CI): 0.18-15.6; p = 0.65, I2 = 69%) and pyelonephritis (OR = 1.13; 95% CI: 0.65-1.99; p = 0.66, I2 = 1%) without significant difference in each group statistically. The pooled study data showed a significantly higher incidence of UEAS (OR = 2.84; 95% CI: 1.75-4.61, p < 0.0001, I2 = 50%) and a lower incidence of vesicoureteral reflux (OR = 0.24; 95% CI: 0.10-0.59; p = 0.002, I2 = 75%) in anti-reflux anastomosis compared to direct anastomosis. In subgroup analysis, anti-reflux anastomosis was more likely to result in UEAS than direct anastomosis, especially when ureteral stent was removed within 14 days. CONCLUSION: Although meta-analysis showed that overall incidence of vesicoureteral reflux was higher with direct anastomosis than anti-reflux anastomosis, the rate of vesicoureteral reflux was not directly related to impairment of RFn. The anti-reflux mechanism of ONB was positively associated with a higher incidence of significant UEAS compared to the direct approach, which can lead to kidney damage and an increased risk of secondary surgical procedures.