Several promising candidate drugs that target bacterial adherence and biofilm formation are being developed. Such hopeful drugs cannot be studied in chronic rhinosinusitis (CRS) without the evaluation of such virulence criteria in different forms of the disease with and without nasal polyposis (CRSwNP and CRSsNP). The aim of this study was to evaluate bacterial adherence, response to antibiotics and degree of accumulation of bacterial biofilms as new targets of treatment in CRSwNP and CRSsNP. Twenty CRS patients and 10 normal subjects with airway obstructing concha bullosa were prospectively enrolled in the present study. Scanning electron microscopy and cultures were performed on paranasal sinus tissue samples. Bacterial adherence tests using the tissue culture plate method were measured quantitatively. Strongly adherent bacteria were identified significantly in 6/9 (77%) cases of CRSsNP in comparison to 1/7 (14%) cases of CRSwNP. Strongly adherent bacteria that were sensitive to ciprofloxacin, vancomycin, and impenim were identified in 75% of the cultured coagulase positive staphylococci. A significant difference (P = 0.007) in the degree of accumulation of bacterial biofilms existed between the two groups. In CRSsNP, a more advanced stage of bacterial biofilms with strong bacterial adherence was observed which make them attractive targets for new drugs. In CRSwNP, lower stage bacterial biofilms with low bacterial adhesion were identified, which may help explain the low bacterial virulence in an environment of suboptimal, organizational arrangements.