Lay Summary Acute kidney injury (AKI) has been associated with increased risks of new-onset and worsening proteinuria. Increased understanding of post-AKI proteinuria will enhance the knowledge about the interconnection between AKI and chronic kidney disease (CKD). In this large multicenter cohort study, we evaluated the incidence, risk factors and clinical correlations of post-AKI proteinuria among hospitalized patients. We found that post-AKI proteinuria is common and usually transient among hospitalized patients. The risk profiles for new-onset and worsening post-AKI proteinuria differed markedly. Higher AKI stage and preexisting CKD were risk factors for both new-onset and worsening proteinuria, but by contrast, treatment of AKI patients with renin-angiotensin system inhibitors significantly reduced the risk of new-onset proteinuria. Worsening proteinuria was associated with a lower incidence of AKI recovery and a higher risk of kidney disease progression, which emphasized the need for close monitoring of proteinuria after AKI. Background Acute kidney injury (AKI) has been associated with increased risks of new-onset and worsening proteinuria. However, epidemiologic data for post-AKI proteinuria was still lacking. This study aimed to determine the incidence, risk factors and clinical correlations of post-AKI proteinuria among hospitalized patients. Methods This study was conducted in a multicenter cohort including patients aged 18-100 years with hospital-acquired AKI (HA-AKI) hospitalized at 19 medical centers throughout China. The primary outcome was the incidence of post-AKI proteinuria. Secondary outcomes included AKI recovery and kidney disease progression. The results of both quantitative and qualitative urinary protein tests were used to define post-AKI proteinuria. Cox proportional hazard model with stepwise regression was used to determine the risk factors for post-AKI proteinuria. Results Of 6206 HA-AKI patients without proteinuria at baseline, 2102 (33.9%) had new-onset proteinuria, whereas of 5137 HA-AKI with baseline proteinuria, 894 (17.4%) had worsening proteinuria after AKI. Higher AKI stage and preexisting CKD diagnosis were risk factors for new-onset proteinuria and worsening proteinuria, whereas treatment with renin-angiotensin system inhibitors was associated with an 11% lower risk of incident proteinuria. About 60% and 75% of patients with post-AKI new-onset and worsening proteinuria, respectively, recovered within 3 months. Worsening proteinuria was associated with a lower incidence of AKI recovery and a higher risk of kidney disease progression. Conclusions Post-AKI proteinuria is common and usually transient among hospitalized patients. The risk profiles for new-onset and worsening post-AKI proteinuria differed markedly. Worsening proteinuria after AKI was associated with adverse kidney outcomes, which emphasized the need for close monitoring of proteinuria after AKI.