BACKGROUND Pancreatic cancer (PC) is a common digestive system tumor. For patients with advanced pancreatic cancer (APC), chemotherapy is still the predominant treatment. However, no large-scale clinical studies have been done of it as first-line therapy for APC. The goal of the present study was to assess real-world outcomes with chemotherapy in that setting. MATERIAL AND METHODS We retrospectively analyzed data from 322 patients with APC who were treated with chemotherapy at 4 hospitals in different cities in China. The first-line regimens used were AS (nab-paclitaxel and S-1), AG (nab-paclitaxel and gemcitabine), and FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin). RESULTS Of the patients, 232 received AS, 79 received AG, and 11 received FOLFIRINOX. The median number of chemotherapy cycles was 5. The median overall survival (mOS) was 9 months and the median progression-free survival (mPFS) was 5 months. The AS, AG, and FOLFIRINOX regimens were associated with mOS rates of 9 months, 9 months, and 10 months, respectively. The mPFS rates for the AS, AG, and FOLFIRINOX regimens were 5, 4, and 5 months, respectively. The differences between the PFS rates for the regimens were statistically significant. The overall response rate (ORR) and overall disease control rate (DCR) for chemotherapy were 38% and 81.8%, respectively. The ORRs for the AS, AG, and FOLFIRINOX regimens were 46.9%, 18.7%, and 0%, respectively. The DCRs for the AS, AG and FOLFIRINOX regimens were 87.2%, 69.3%, and 63.6%, respectively. The differences between the ORRs and DCRs for the regimens were statistically significant. The incidences of grade 3/4 adverse events (AEs) associated with the AS, AG, and FOLFIRINOX regimens were 29.9%, 25%, and 36.4%, respectively. CONCLUSIONS The AS regimen was associated with a higher ORR and DCR than the other 2 regimens, with a lower rate of AEs.