The aim of this study was to investigate the features, treatment, and prognosis of early versus late recurrence of centrally located hepatocellular carcinoma (CL-HCC) after mesohepatectomy (MH).Three hundred forty eight patients with CL-HCC undergoing MH were included. Data on clinicopathological characteristics, initial surgical details, timing and sites of tumor recurrence, management after recurrence, and long-term outcomes were analyzed.The optimal cutoff value to differentiate early (71 patients, 64.5%) versus late (39, 35.5%) recurrence was defined as 12 months. Patients with early recurrence (ER) had higher alpha fetoprotein (AFP) level (P < .001), more advanced tumor stage (P = .024), and higher incidence of microvascular invasion (MVI, P = .001). Patients with ER had higher incidence of local tumor recurrence (P = .027) and higher average number of recurrent nodules (P = .016) than patients with LR. Patients after ER showed a better overall survival (from date of diagnosis of recurrence) than after late recurrence (LR). Patients with ER had less chances of curative treatment (14.1% vs 41.0%, P = .004) after tumor recurrence than patients with LR. Multivariable analyses revealed that liver cirrhosis (P < .001) and tumor differentiation (P < .001) were associated with an increased likelihood of LR, while multiple tumor number (P = .005), type IV classification (P = .012), and MVI (P < .001) were independent risk factors related to ER.ER and LR after MH for CL-HCC were associated with different risk predictors and prognosis. Data on the timing of recurrence may inform decisions about postoperative adjuvant treatment, as well as help to predict long-term survival for these patients.