The purpose of this study was to compare the "caudal to cranial" (CC) versus "medial to lateral" (ML) approach for laparoscopic right hemicolectomy. Pertinent data from all patients with stage II and III between January 2015 and August 2017 were entered into a retrospective database. A total of 175 patients underwent the ML (N = 109) or CC approach (N = 66). Patient characteristics were equivalent between groups. The CC group showed a shorter surgical time 170.00 (145.00, 210.00) vs. (206.50 (178.75, 226.25) min) than the ML group (p < 0.001). The time to oral intake was shorter in the CC group than in the ML group ((3.00 (1.00, 4.00) vs. 3.00 (2.00, 5.00) days; p = 0.007). For the total harvested lymph nodes, there was no statistical significance between the CC group 16.50 (14.00, 21.25) and the ML group 18.00 (15.00, 22.00) (p = 0.327), and no difference was found in the positive harvested lymph nodes (0 (0, 2.00) vs. 0 (0, 1.50); p = 0.753). Meanwhile, no differences were found in other perioperative or pathological outcomes, including blood loss and complications. For 5-year prognosis, overall survival rates were 75.76% in the CC group and 82.57% in the ML group (HR 0.654, 95% CI 0.336-1.273, p = 0.207); disease-free survival rates were 80.30% in the CC group and 85.32% in the ML group (HR 0.683, 95% CI 0.328-1.422, p = 0.305). Both approaches were safe and feasible and resulted in excellent survival. The CC approach was beneficial in terms of the surgical time and time to oral intake.