Patients with nasopharyngeal carcinoma (NPC) benefit from antibiotics when there are infective complications during and around chemoradiotherapy, but there is some indication that antibiotics used peri treatment may affect patients' outcomes. Here we sought to elucidate the exact impacts of antibiotics on NPC patients' outcomes around primary treatment. This was a retrospective cohort study in a tertiary academic center in Hong Kong SAR. NPC patients treated for primary disease between 2010 and 2014 were evaluated for the impact of antibiotics prescribed around primary treatments on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS), which was analyzed by multivariate Kaplan–Meier and Cox Proportional Hazard Regression analysis. The data were analyzed and performed with SPSS, V27.0 and GraphPad, V8.0 A total of 455 patients with primary NPC were included in the study. The cohort consisted of predominantly males (75.6%). Patients who had advanced tumor stage (p=0.019), received NC (p=0.008) or CCRT (p=0.002), were more likely to be prescribed antibiotics. On univariate analysis smoking (p=0.02), advanced stage of disease (p=0.007), lymph node metastasis (p= 0.004), NC administration (P<0.001) and antibiotic use was associated with a poorer year DSS in NPC patients. Antibiotic use around primary NPC treatment (5-year: HR 1.644 95%CI [1.015, 2.665], 10-year: 1.640 [1.085, 2.480]), within 2 weeks (5-year: 1.685 [1.015, 2.799], 10-year: 1.600 [1.030, 2.486]) or 1 week (5-year: 1.811 [1.073, 3.055]), were associated with significantly worse DSS in NPC patients, Figure 1 shows the Kaplan Meir curves. The negative elements included using specific antibiotics (5-year: 2.53 [1.331, 4.807], 10-year: 2.215 [1.236, 3.969]) and oral administration as well (5-year: 1.731 [1.069, 2.805], 10-year: 1.647 [1.087, 2.497]). Multivariate analysis showed a trend towards worse DSS at 5 years with antibiotic use at 1 week around therapy (P=0.054). [Display omitted] In NPC, antibiotics use around primary treatment, regardless of stage, had a poorer prognosis, especially disease-specific survival. In clinical practice, events leading to the prescription of antibiotics or the administration of antibiotics should be carefully considered in NPC patients treated for primary NPC. [ABSTRACT FROM AUTHOR]