Background: The facilitation of early recovery of acute kidney injury (AKI) is an important step to improve outcome, particularly because of the limited therapeutic interventions currently available for AKI. The combination of an electronic alert and biomarker-guided kidney-protection strategy implemented in the routine care may have an impact on the incidence of early complete reversal of AKI after major non-cardiac surgery. Methods: We studied 294 patients in two cohorts before (n = 151) and after protocol implementation (n = 143). Data collection required 6 months for each cohort. The kidney-protection protocol included an electronic alert to detect patients who were eligible for urinary biomarker [TIMP2 x IGFBP7]-guided kidney-protection intervention. Intervention was stratified according to three levels of immediate AKI risk: low, moderate, and high. After intervention, postoperative changes in the glomerular filtration rate (eGFR) were identified with a tracking software that included an alert for nephrology consultation if the eGFR had declined by > 25% from the preoperative reference value. Primary outcome was early AKI recovery, i.e., the complete reversal of any AKI stage to absence of AKI within the first 7 postoperative days. Results: Protocol implementation significantly increased the recovery of AKI (36/46, 78% compared to control 27/48, 56%, (p = 0.025)) and reduced the length of the ICU stay (p < 0.001). There was no significant difference in the overall incidence of all AKI and moderate and severe AKI in the first 7 postoperative days: 46/143 (32%) and 12/151 (8%) in the protocol implementation group compared to 48/151 (32%) and 18/151 (12%) in the historical control group. Patients with AKI reversal within the first 7 postoperative days had lower in-hospital mortality than patients without AKI reversal. Conclusions: Implementing a combined electronic alert and biomarker-guided kidney-protection strategy in routine care improved early recovery of AKI after major surgery.