Background: Pancreatic acinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas. Because of its rare incidence, efficacy of chemotherapy in this patient population still remains largely unknown. Therefore, we retrospectively analyzed the outcomes of patients with pancreatic ACC who received chemotherapy. Methods: Between January 1997 and March 2015, a total of 22 patients with histologically confirmed locally advanced unresectable or metastatic pancreatic ACC were identified in Asan Medical Center, Seoul, Korea. Among them, 15 patients received chemotherapy and 2 patients with locally advanced disease underwent concurrent chemoradiotherapy followed by chemotherapy; these 17 patients were included in this analysis. Results: Median age was 58 year old (range, 29-72), and 15 patients (88%) were male. Mixed acinar-neuroendocrine tumor and mixed acinar-adenocarcinoma was found in 1 (6%) and 2 (12%) patients, respectively. The most common metastatic site was liver (n = 9, 53%), followed by intraabdominal lymph nodes (n = 5, 29%), and peritoneum (n = 3, 18%). As 1^st-line therapy, 5-FU or its derivative were given in 7 patients (41%), gemcitabine in 6 (35%), gemcitabine plus capecitabine in 2 (12%) and FOLFOX in 2 (12%). Objective response rate (ORR) was 30% and median time-to-progression (TTP) was 5.8 months (95% CI, 2.9-8.6). After progression, 2^nd-line chemotherapy was given in 9 patients; 5 and 4 patients received FOLFOX and gemcitabine, respectively. On 2^nd-line chemotherapy, ORR was 44% and median TTP was 6.3 months (95% CI, 0.3-12.4); patients with FOLFOX had significantly better TTP compared to those with gemcitabine (median 6.5 vs 1.4 months, p = 0.003). The ratio of TTP at 1^st-line chemotherapy to TTP at 2^nd-line chemotherapy was significantly higher in patients with FOLFOX (2.10 [range, 0.16-8.30] compared to those with gemcitabine (0.12 [0.08-0.25]; p = 0.03). Median overall survival in all patients was 16.9 months (95% CI, 14.4-19.4). Conclusions: Pancreatic ACC seems to have better prognosis compared to pancreatic adenocarcinoma. Our results suggest that oxaliplatin-containing regimen may have improved activity against pancreatic ACC.