Background: To improve the poor prognosis of patients with pancreatic cancer, we examined the effect of 6 months of neoadjuvant chemotherapy (NAC) using gemcitabine and S1 before surgery and found significantly prolonged survival. Clinical use of this treatment is expected in the future. However, preoperative NAC may increase the physical burden on patients as well as their psychological burden due to the longer waiting time. Thus, it is necessary to confirm that the treatment does not reduce quality of life (QOL). Methods: In this observational study of patients who underwent resection after this NAC, a QOL questionnaire survey was administered preoperatively and at postoperative months 3, 6, and 12, to consenting patients from those enrolled in randomized controlled trials (RCTs). The intervention group (planned surgery and NAC) had added pre- and post-treatment QOL surveys. We used the Short Form 36 Health Survey version 2 (SF-36v2 Standard, Japanese) to measure health-related QOL. Overall differences among the groups were evaluated by paired t test and two- and three-way ANOVA. All statistical analyses were performed using SPSS (ver. 21) software. Results: In total, 55 patients (mean age 66.0 years), about 15% of those enrolled in the RCTs, responded to the questionnaire (NAC group, n = 22; control group, n = 33). QOL was not significantly reduced in the NAC group pre- and post-treatment (p= 0.19-0.96). Notably, there were no significant differences in post-treatment QOL, with improvement in the Physical Functioning (75.9→79.4), Bodily Pain (70.5→72.5), Vitality (59.6→59.9), and Mental Health (66.5→69.7) SF-36 domains compared with before preoperative treatment. This suggests that patients had good preoperative physical and mental QOL. QOL at each time point did not differ significantly in the 8 domains with or without NAC; the Mental component summary score was significantly higher in the NAC group compared with the control group at 3 months (54.9 vs 49.3, p= 0.04). NAC and QOL did not differ significantly by time, sex, and operation type. Conclusions: NAC using gemcitabine and S1 before surgery for pancreatic cancer does not reduce QOL. Improved prognosis can be expected with no adverse effect on QOL.