Direct Immunofluorescence (DIF) is invaluable in the diagnosis of cutaneous vesiculobullous lesions (VBL). It is limited by technical factors and disease nature. 1) To record the sensitivity of DIF in VBL 2) To correlate DIF with clinical, histologic findings and analyse discrepancies.A retrospective study of 100 DIFs on suspected VBL of skin. DIF, histology and clinical data were reviewed. 73/100 cases showed DIF patterns concordant with clinical/histologic diagnosis. The sensitivity of DIF was 88% in Pemphigus group (39/ 44), 82% in Bullous Pemphigoid (BP) (23/28), and 20% in Dermatitis Herpetiformis (DH) (1/5).18 cases of histologically proven VBL were negative and of these, 4 had no epidermis. The remaining 9 cases were discordant with clinical/histologic features, including 4 BP and 5 DH, whose histology was non-specific and will be discussed in detail. One case of DH showed an aberrant vasculitic pattern. DIF is of great value in the diagnosis of VBL, specially in clinical/histologic dilemmas. In DH, neither biopsy nor DIF were very useful and response to therapy was the standard. Sampling errors contributed to false negative results. Proper selection of cases and judicious use are mandatory to optimize its' utility.