Objectives To elucidate the significance of intrarenal reflux. Methods We retrospectively analyzed 276 patients (age <5 years) with grade III to V vesicoureteral reflux. They were divided into two groups: 55 patients with intrarenal reflux and 221 patients without intrarenal reflux (control group). All patients received low-dose antibiotic prophylaxis. Results The most common initial presentation in both groups was febrile urinary tract infection. On dimercaptosuccinic acid scan, the rate of decreased differential renal function (<40%) was significantly higher in the intrarenal reflux group than in the control group (51% vs 33%, P<0.05). Breakthrough urinary tract infections were observed in 26 patients (47%) in the intrarenal reflux group and 61 patients (28%) in the control group (P<0.01). There was no statistically significant difference regarding spontaneous resolution of reflux, which occurred in nine patients (16%) in the intrarenal reflux group and 32 patients (14%) in the control group. Surgical treatment was selected more often in the intrarenal reflux group (P<0.05) because of the high incidence of breakthrough urinary tract infection. Conclusions The rate of spontaneous resolution of high-grade vesicoureteral reflux is similar between patients with and without intrarenal reflux. However, those with intrarenal reflux present are more likely to present a decreased differential renal function and breakthrough urinary tract infections. Consequently, surgical treatment is considered more frequently in cases with intrarenal reflux. Although high-grade vesicoureteral reflux with intrarenal reflux can be treated conservatively, physicians should take into account the higher risk of breakthrough urinary tract infections.