The presence of unilateral vesicoureteral reflux (VUR), and renal dysplasia associated with posterior urethral valves (PUV) (VURD syndrome) was believed to represent a pressure-released pop-off mechanism protecting kidney function. We aimed to investigate its role with respect to long-term kidney function in a cross-sectional and longitudinal analysis. We compared the iohexol glomerular filtration rate (GFR) measured at 5 (GFR5) and 10 (GFR10) years of age in children with (Group A) and without (Group B) VURD syndrome, who underwent PUV resection under 2 years of age. VURD syndrome was diagnosed in cases of unilateral loss of kidney function (<15% on nuclear medicine test) associated with ipsilateral grade IV-V VUR. VURD syndrome was diagnosed in 16 (12.8%) out of 125 patients who met the inclusion criteria. While the median GFR5was similar in the 2 groups [Group A: 87.3 (74.7–101.2) mL/min/1.73 m2vs. Group B: 99.6 (77–113) mL/min/1.73 m2,p-value: 0.181], the median GFR10values were significantly lower in children with VURD syndrome [Group A: 75.7 (71.2–85.9) mL/min/1.73 m2vs. Group B: 95.1 (81.2–114.2) mL/min/1.73 m2,p-value: 0.009]. Similar results were obtained in a longitudinal analysis of the children with GFR measurement available both at 5 and 10 years of age [GFR5in Group A: 93.1 (76.9–103.5) mL/min/1.73 m2vs. Group B: 97.5 (80–113) mL/min/1.73 m2,p-value: 0.460; GFR10: Group A: 71.9 (71.9–85.9) mL/min/1.73 m2vs. Group B: 94.8 (81.5–110.6) mL/min/1.73 m2,p-value: 0.024]. In conclusion, VURD syndrome does not show a protective role in kidney function preservation. On the contrary, it seems to be associated with a deterioration of the kidney function on a long-term follow-up.