© 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc. Background The systemic inflammatory response may be associated with tumor progression. We sought to analyze the impact of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on recurrence-free survival (RFS) and disease-specific survival (DSS) among patients who underwent surgery for adrenocortical carcinoma (ACC). Methods Patients undergoing surgery for ACC were identified from a multi-center database. Cut-off values of 5 and 190 were defined as elevated NLR and PLR, respectively, and long-term outcome was assessed. Results Among 84 patients with ACC, 29 (34.%) had NLR>5 while 32 (40.5%) had PLR>190. NLR and PLR were associated with larger tumors (NLR>5: ≤5cm, 0% vs. >5cm, 39.7%; PLR>190: ≤5cm, 0% vs. >5cm, 45.7%), as well as need to resect of other organs (NLR>5: other organ resected 48.8% vs. not resected 20.9%; PLR>190: other organ resected 25.0% vs. not resected 56.4%)(all P<0.05). Five-year RFS was associated with an elevated NLR (NLR≤5, 14.2% vs. NLR>5, 10.5%) and PLR (PLR≤190: 19.4% vs. PLR>190: 5.2%) (both P<0.05). On multivariate survival analyses, PLR remained a predictor of RFS (HR 1.72), while NLR was associated with both DSS (HR 2.21) and RFS (HR 1.99) (both P<0.05). Conclusions Immune markers such as NLR and PLR may be useful to stratify patients with regards to prognosis following surgery for ACC. J. Surg. Oncol. 2015 111:164-172.