Background: Icodextrin is a high molecular weight, starch-derived glucose polymer that is used as an osmotic agent in peritoneal dialysis (PD) to promote ultrafiltration. There has been wide variation in its use across Australia and the rest of the world, but it is unclear whether these differences are due to patient- or centre-related factors. Methods: Using the Australia and New Zealand Dialysis and Transplant Registry, all adult patients (>18 years) who started PD in Australia between 1 January 2007 and 31 December 2014 were included. The primary outcome was icodextrin use at PD commencement. Hierarchical logistic regression clustered around the treatment centre was applied to determine the patient- and centre-related characteristics associated with icodextrin use. The impact of centre-level practice pattern variability on icodextrin uptake was estimated using the intra-cluster correlation coefficient (ICC). Results: Of 5948 patients starting on PD in 58 centres during the study period, 2002 (33.7%) received icodextrin from the outset. Overall uptake of icodextrin increased from 29% in 2010 to 42.5% in 2014. Patient-level characteristics associated with an increased likelihood of commencing PD with icodextrin included male sex (adjusted odds ratio (OR) 1.55, 95% confidence interval (CI) 1.35–1.77; p < 0.001), prior haemodialysis or kidney transplantation (OR 1.26, 95% CI 1.09–1.47), obesity (OR 1.66, 95% CI 1.41–1.96), diabetes mellitus (OR 2.32, 95% CI 2.03–2.64) and residing in a postcode with the highest decile of socio-economic status (OR 1.43, 95% CI 1.11–1.85). The centre-level characteristic associated with an increased likelihood of commencing PD with icodextrin was routine assessment of a peritoneal equilibration test (OR 1.45, 95% CI 1.27–1.66). Centres with fewer patients on automated peritoneal dialysis (APD) were less likely to start on icodextrin (APD proportion <57%; OR 0.45, 95% CI 0.20–0.99). Centre factors accounted for 25% of the variation in icodextrin use solution among incident PD patients (ICC 0.25). Conclusions: Icodextrin use in incident Australian PD patients is increasing variable and associated with both patient and centre characteristics. Centre-related factors explained 25% of variability in icodextrin use.