Background: Fracture-Related Infection (FRI) is a challenging complication after surgical fracture treatment. Consequences include reoperations, increased medical costs, loss of function and even amputation. Objectives: This study aimed to analyze the rate, predictors of infection, clinical-radiological presentation and microbial profiles of open tibia FRI. Methods: Between January 2022 and June 2022, a descriptive cross-sectional observational study was conducted at Muhimbili Orthopaedic Institute (MOI) involving patients aged 18 years and above with surgically managed open tibial shaft fractures in the preceding 12 months. Microbiological culture of three intraoperative tissue and bone specimens were taken by sterile techniques using separate and sterile instruments. Results: There were 190 patients between 18-72 years with a mean age of 35.6 ±10 years. After surgical debridement, all 190 (100%) were managed with either an external fixator or an intramedullary nail. It was found, 49 (25.8%) patients had FRI. A smoking history was identified as a predictor of infection (AOR= 2.21 95% CI 0.84-5.59, P value 0.108). Delayed union was a complication found in 70.3% of patients with infection attending 12th week follow-up and beyond. Almost all (96.5%) intraoperative tissue samples were culture positive, yielding most isolates as polymicrobial (57.9%) and the predominant pathogen identified being Gram-negative bacteria in delayed and late infections. Conclusion: About one-quarter of open tibial shaft fractures are at risk of FRI. The risk is higher among smokers. Intraoperative tissue sampling provides significant cultural yield with predominant gramnegative infection in delayed and late presentation.