Background: The Naples prognostic score (NPS) is a scoring system that reflects a patient’s systemic inflammatory and nutritional status. This study aimed to evaluate whether postoperative NPS is effective in assessing the prognosis of stage II–III colorectal cancer (CRC) patients compared with preoperative NPS. Methods: Between 2005 and 2012, a total of 164 patients diagnosed with stage II–III CRC, who underwent curative resection followed by adjuvant chemotherapy, were divided into two groups: Group 0–1 (NPS = 0–2) and Group 2 (NPS = 3 or 4). Preoperative NPS was calculated based on the results before surgeries, and postoperative NPS was assessed using the results obtained before adjuvant chemotherapy. Results: The overall survival of Group 0–1 was higher than that of Group 2 in both pre- and postoperative NPS assessments. According to the ROC curve analysis, the Area Under the Curve (AUC) ratio for postoperative NPS was 0.64, compared with 0.57 for preoperative NPS, 0.52 for the preoperative neutrophil–lymphocyte ratio (p = 0.032), and 0.51 for the preoperative platelet–lymphocyte ratio (p = 0.027). Conclusions: Postoperative NPS is effective in predicting the prognosis of stage II–III CRC patients who underwent curative resection followed by adjuvant chemotherapy. The use of NPS could be beneficial in evaluating the prognosis of CRC patients after surgeries.