<i>Moraxella catarrhalis</i>, a less virulent microorganism that colonizes the upper respiratory tract, has recently been associated with lower respiratory disease, especially in HIV-positive immunocompromised individuals and children. Here, we correlated the DNA clustering pattern of 24 clinical isolates of <i>M. catarrhalis</i> for β-lactamase production and drug resistance, from different disease groups using three different arbitrarily selected primers, P1 (5′-TCACGATGCA-3′), P14 (5′-GATCAAGTCC-3′) and P17 (5′-GATCTGACAC-3′). <i>M. catarrhalis </i>revealed three distinct banding patterns with primer P1, four with P14 and P17. 71% (n = 17) of the isolates revealed pattern 2 with primer P1, which discriminated majority (12/21) of the isolates grouped under the major branch of the dendrogram. The minor branch had only three isolates. Separation of <i>M. catarrhalis</i> into two subpopulations (major and minor clusters) with primer P1 is suggestive of diverse genetic lineage. A high level of concordance between RAPD and antibiotic profile was observed. Clustering of <i>M. catarrhalis</i> recovered from different disease groups reflect the identical clinical background or the common geographical/temporal factors. The presence or absence of β-lactamase in a cluster confirmed their single source of origin.