A total of eighty-one Escherichia coli isolates belongs to forty-three different serotypes including several pathogenic strains such as enterotoxigenic E. coli (ETEC), enterohaemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC) and uropathogenic E. coli (UPEC) isolated from a tropical estuary were tested against 12 antibiotics to determine the prevalence of multiple antibiotic resistance (MAR), antimicrobial resistance profiles and also to find out high risk source of contamination by MAR indexing. The results revealed that more than 95% of the isolates were multiple antibiotic resistant (resistant to more than three antibiotics). Resistance to vancomycin, novobiocin, kanamycin, oxytetracycline, tetracycline, streptomycin was high (>80%), resistance to other antibiotics was relatively less. The MAR indexing of the isolates showed that all these strains were originated from high risk source of contamination. The incidence of multiple antibiotic resistant E. coli especially the pathogenic strains in natural water will pose a serious health risk to the human population and also act as a `manmade' reservoir of resistance genes for (potentially) pathogenic bacteria. The determination of antibiotic susceptibility/resistance patterns of isolated microbes is a part of the microbial monitoring process of the water which would be important for the meaningful interpretation of sanitary water quality data.