Objective: The aim of this study was to systematically compare the perioperative outcomes of percutaneous nephrolithotomy in patients with or without previous ipsilateral open renal surgery (POS). Design: Systematic searches of the PubMed, Web of Science and Cochrane Library databases were used to identify relevant studies, and, following literature screening and data extraction, a meta-analysis was performed. Results: 17 retrospective cohort studies involving 4833 procedures (4784 patients) were included. No statistically significant differences were observed between patients with or without POS in terms of supracostal access; single/multiple tracts; metal dilator need; time required to access the collecting system; fluoroscopic duration; demand for analgesics; hospital stay; final stone-free rate; and risk of developing certain complications (eg, fever, haemorrhage, haemo/hydro/pneumothorax, blood transfusion, urinary tract infection and sepsis) as well as regarding the risk of total complications. Patients with POS, however, had a greater drop in haemoglobin (weighted mean difference (WMD), 1.78 g/L; 95% CI 1.09 to 2.47; p<0.00001) and higher risk of bleeding that required angiographic embolisation (relative risk (RR), 3.73; 95% CI 1.36 to 10.21; p=0.01). In addition, patients with POS also had a lower initial stone-free rate (RR, 0.96; 95% CI 0.92 to 0.99; p=0.007) and more secondary treatment (RR, 1.61; 95% CI 1.09 to 2.37; p=0.02). Sensitivity analysis produced comparable results except for differences in operative time and initial stone-free rate, which did, however, prove to be statistically insignificant (p=0.16 and 0.69, respectively). Conclusions: Current evidence suggests that percutaneous nephrolithotomy in patients with POS is associated with a significantly greater drop in haemoglobin, higher risk of requiring angiographic embolisation and auxiliary procedures, potentially longer operative time, and lower initial stone-free rate than percutaneous nephrolithotomy in patients without POS.