Introduction Open tibia fractures are among the most challenging orthopedic injuries, often associated with high rates of complications such as infection, non-union, and delayed healing. These fractures typically result from high-energy trauma, such as motor vehicle accidents or falls from significant heights, and are frequently accompanied by soft tissue damage and contamination. Open tibia fractures are among the most common orthopedic injuries, often requiring surgical intervention. This study compares clinical and radiological outcomes between uncoated and antibiotic-coated intramedullary interlocking nails in managing open tibia fractures. Material and Methods A prospective comparative study was conducted in the Department of Orthopedics, VRK Institute of Medical Sciences, Teaching Hospital & Research Centre over a period of 1 year at our institution, involving patients diagnosed with open tibia fractures. This was a randomized controlled trial involving patients aged 18–60 years with open tibia fractures classified as Gustilo-Anderson types I–III11. Ethical approval was obtained from the institutional review board, and informed consent was acquired from all participants. Patients were randomly assigned into two groups: uncoated IMIL (Group A) and antibiotic-coated IMIL (Group B). Standard preoperative protocols, including intravenous antibiotic prophylaxis and wound debridement, were followed. Results Group B (antibiotic-coated IMIL) demonstrated a significantly lower infection rate (8%) compared to Group A (24%, p = 0.03). This finding highlights the potential benefit of antibiotic-coated nails in reducing postoperative infections, particularly in open tibia fractures, which are prone to contamination. Patients in Group B consistently achieved better functional outcomes at all postoperative time points (6, 12, and 24 weeks) compared to Group A (p < 0.05). At 6 weeks postoperatively, a significantly higher proportion of patients in Group B (76%) showed evidence of fracture healing compared to Group A (60%, p = 0.04).  Conclusion Antibiotic-coated intramedullary interlocking nails offer significant advantages in reducing infection rates and improving clinical outcomes in open tibia fractures. Their use can be a valuable addition to the standard treatment protocol, especially in high-risk cases.