Background: The role of viruses in chronic rhinosinusitis (CRS) is poorly understood. In part, this is secondary to difficulty in isolating viruses. Although traditional detection methods for respiratory viruses have had little clinical utility, modern viral screening techniques that use molecular sequencing are now both rapid and feasible, which makes analysis of the paranasal sinus microbiome more accessible. Objective: To detect respiratory viruses in the paranasal sinuses of patients with CRS and of healthy controls as well as to correlate clinical and radiographic measures of CRS with viral presence. Methods: In this prospective study, 13 patients with CRS with nasal polyposis (CRSwNP) and 8 patients without nasal polyposis (CRSsNP) were enrolled and compared with 14 healthy controls. Samples were obtained from the paranasal sinuses and were screened for viral DNA with polymerase chain reaction-based sequencing techniques. Typical symptoms of CRS, the Sinonasal Questionnaire, and objective measures, including the modified Lund-Mackay and modified Lund-Kennedy scores were obtained. Results: Eighty percent of the positive screens (4/5) were found in patients with CRSsNP, whereas 20% of the positive tests (1/5) were in the CRSwNP group, and none of the controls tested positive (p = 0.0029). Coronavirus was the most common virus detected. Sinonasal Questionnaire scores of the patients with CRS who tested positive for viruses were higher but not statistically different than those without a positive screen (p = 0.31). Radiographic and endoscopic measures of disease were not significantly different in the setting of a positive viral screen (p = 0.12 and 0.11 respectively). Conclusion: Although traditionally difficult, advances in molecular sequencing enhance detection of viruses in the sinonasal tract. In this study, respiratory viruses were more commonly isolated from patients with CRS compared with healthy controls. Moreover, viral infection may play a greater role in symptom exacerbation in CRSsNP than in CRSwNP. These findings warrant further investigation into the role of the viral microbiome in CRS.