Background The incidence of postoperative morbidity after pancreaticoduodenectomy (PD) is high; however, whether fluid management after surgery affects postoperative morbidity is unclear. This study aimed to determine whether fluid balance in patients undergoing PD is associated with postoperative complications and mortality. Methods Data from a computer-based database of patients who underwent PD between 2016 and 2019 were retrospectively analyzed. Patients were stratified into four quartiles according to their fluid balance at 0–24, 24–48, 48–72, and 72–96 h after surgery. The predefined primary outcome measures were morbidity and mortality rates. Results A total of 301 patients were included. The morbidity and mortality rates in the cohort were 56.5% and 3.7%, respectively. The most common complications after PD were postoperative pancreatic fistula (31.9%) and delayed gastric emptying (31.6%). Patients with a higher fluid balance in the 0–24-, 24–48-, and 48–72-h postoperative periods had a higher morbidity rate and longer hospital stay than those with a lower fluid balance (all P < 0.05). Patients with a fluid balance of 4212 mL during the postoperative 0–72 h were most likely to develop complications (P < 0.001). The area under the receiver operating characteristic curve was 0.71 (0.65–0.77), with a sensitivity of 58.24% and a specificity of 77.10%. Conclusions Higher postoperative fluid balance seems to be associated with increased morbidity after PD compared to lower fluid balance. Surgeons should pay close attention to the occurrence of complications in patients with a high fluid balance.