Cow milk could be used to reduce malnutrition since it is highly nutritious, and many people in Bujumbura city for survival. However, the risk of food contamination by antibiotic residues is one of the significant problems facing public health, and is a result of the irresponsible use of veterinary drugs. This study evaluated antibiotic residues and resistance in milk samples to assess contamination levels and resistance patterns among E. coli isolates. Cross section study design and purposive sampling method was used in selection of area and sample collection. Thirty samples from traditionally heat-treated fresh milk sold in local restaurants were collected each 250mls and transported to National Veterinary Laboratory of Burundi. The detection of antibiotic residue was done by using SNAP duo Test Plus test (IDEXX) which detects beta lactams and tetracycline residue including cephalexin at or below established maximum residue limits. Out of 30 milk samples tested, 16.7% were positive for antibiotic residues, with beta-lactam detected in one sample and tetracyclines in four. Although contamination levels were relatively low, the findings raise concerns about improper veterinary drug management at the farm level. Antibiotic resistance analysis revealed high resistance among E. coli isolates to Ampicillin and Tetracycline, commonly used in the dairy industry and human medicine. Frequent usage of these antibiotics creates selective pressure, promoting the survival of resistant strains. The study underscores the critical need for stricter regulations and improved antibiotic management practices in dairy farming to reduce contamination risks and curb the spread of antibiotic-resistant bacteria. Enhanced monitoring systems and responsible handling of veterinary drugs are essential to ensure food safety and protect public health.