<b><i>Background/Aims:</i></b> Proteinuria is a risk marker for progression of chronic kidney disease (CKD) and treatment with an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) is beneficial in these patients. However, little is known about proteinuria and ACEi/ARB treatment in patients on specialized predialysis care. Therefore, we investigated the association of urinary protein excretion (UPE) and ACEi/ARB treatment with renal function decline (RFD) and/or the start of renal replacement therapy (RRT) in patients on predialysis care. <b><i>Methods:</i></b> In the PREPARE-1 cohort, 547 incident predialysis patients (CKD stages IV–V), referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included (1999–2001) and followed until the start of RRT, mortality, or January 1, 2008. The main outcomes were rate of RFD, estimated as the slope of available eGFR measurements, and the start of RRT. <b><i>Results:</i></b> Patients with mild proteinuria (>0.3 to ≤1.0 g/24 h) had an adjusted additional RFD of 0.35 ml/min/1.73 m²/month (95% CI: 0.01; 0.68) and a higher rate of starting RRT [adjusted HR: 1.70 (1.05; 2.77)] compared with patients without proteinuria (≤0.3 g/24 h). With every consecutive UPE category (>1.0 to ≤3.0, >3.0 to ≤6.0, and >6.0 g/24 h), RFD accelerated and the start of RRT was earlier. Furthermore, patients starting (n = 16) or continuing (n = 133) treatment with ACEi/ARBs during predialysis care had a lower rate of starting RRT compared with patients not using treatment [n = 152, adjusted HR: 0.56 (0.29; 1.08) and 0.90 (0.68; 1.20), respectively]. <b><i>Conclusion:</i></b> In patients on predialysis care, we confirmed that proteinuria is a risk marker for the progression of CKD. Furthermore, no evidence was present that the use of ACEi/ARBs is deleterious.