Introduction Laparoscopic distal pancreatectomy (LDP) is a safe and effective procedure; however, its impact on perioperative inflammatory reactions compared with open distal pancreatectomy (ODP) remains unclear. This study aimed to assess short-term outcomes following LDP and ODP regarding inflammatory reactions. Methods This retrospective study of 77 consecutive patients who underwent distal pancreatectomy for low-grade malignancies between 2005 and 2022 compared white blood cell (WBC) count, C-reactive protein (CRP) level, serum albumin level, and CRP/albumin ratio (CAR) between LDP and ODP. Complications, especially postoperative pancreatic fistula (POPF), recovery program, and hospital stay period were also compared. Results POPF (17.1% vs. 38.7%, p = 0.039) and surgical morbidity (≥Clavien-Dindo Grade III, 12.2% vs. 32.3%, p = 0.038) were significantly lower in LDP than in ODP, as for the difference in postoperative inflammatory response, including CRP and CAR, was just temporary. By multivariate analysis, CAR≥6.94 on POD 3 was significant predictor of POPF (42.1% vs. 13.2%, Odds ratio 4.828, p=0.030) Conclusion LDP has lower POPF and earlier postoperative recovery. CAR could be a predictor of POPF.