Nosocomial infections are infections acquired by a patient as a result of treatment in a hospital or healthcare service providing center and symptoms occurs within a short period of hospitalization. The study was to determine the antibiotic resistance patterns of Escherichia coli isolated from Kumasi-South, Tafo and Suntreso Hospitals, Kumasi, Ghana. Total of 600 swabs samples from the hospitals were collected between January and June, 2010. The isolates were identified using morphological and biochemical means. A total of 97 E. coli isolates were obtained from the hospitals. Beds in hospital wards had the highest number of E. coli strains (53.6%), followed by floors (20.6%) while drainages had the least isolates (3.1%). Majority of the E. coli isolates (90.7%) exhibited resistance to ampicillin while 6.2 and 3.1% showed intermediate and sensitive respectively. Co-trimoxazole, 78.4% of the isolates were resistant while 9.3 and 12.4% exhibited intermediate and sensitive responses respectively. E. coli isolates (28.6 to 46.4%) were resistant to gentamicin, ciprofloxacin and ceftriaxone while 14.4 to 47.4% gave intermediate responses. Most isolates (80.4%) exhibited multi-drug resistance. There is a need to observe proper personal hygiene, use of effective disinfectants and proper disposal of contaminated/pathogenic materials in these hospitals to control nosocomial infections.