Point-of-care ultrasonography (POCUS) with concomitant venous and arterial Doppler assessment enables clinicians to assess organ-specific blood supply. To date, no studies have investigated the usefulness of including a comprehensive perioperative POCUS assessment of patients undergoing major laparoscopic surgery. The primary aim of the present study was to evaluate whether the combined venous and arterial renal flow evaluation, measured at different time points of perioperative period, may represent a clinically useful non-invasive method to predict postoperative acute kidney injury (AKI) after major laparoscopic urologic surgery. The secondary outcome was represented by the development of any postoperative complication at day 7. We included 173 patients, subsequently divided for analysis depending on whether they did (n = 55) or did not (n = 118) develop postoperative AKI or any complications within the first 7 days. The main results of the present study were that: (1) the combination of arterial hypoperfusion and moderate-to-severe venous congestion inferred by POCUS were associated with worst outcomes (respectively, HR: 2.993, 95% CI: 1.522–5.884 and HR: 8.124, 95% CI: 3.542–18, p < 0.001); (2) high intra-operative abdominal pressure represents the only independent determinant of postoperative severe venous congestion (OR: 1.354, 95% CI: 1.017–1.804, p = 0.038); (3) the overall number of complications relies on the balance between arterial inflow and venous outflow in order to ensure the adequacy of peripheral perfusion; and (4) the overall reliability of splanchnic perfusion assessment by Doppler is high with a strong inter-rater reliability (ICC: 0.844, 95% CI: 0.792–0.844). The concomitant assessment of arterial and venous Doppler patterns predicts postoperative complications after major laparoscopic urologic surgery and may be considered a useful ultrasonographic biomarker to stratify vulnerable patients at risk for development of postoperative complications.