Effective health service delivery hinges on the interface between professionals rendering health services to the sick and the injured. This paper examined the inter-professional collaboration and knowledge management practices among the clinical workforce in Federal Tertiary Hospitals in three Geopolitical Zones of Nigeria. The study employed a non-experimental survey design. 550 questionnaires were administered out of which 479 were completed for analysis comprising 204 Medical Doctors, 180 Nurses and 95 Health Information Management Officers, which resulted into 87% response rate. Findings from the study revealed that knowledge acquisition was the most practiced, closely followed by knowledge application. In addition, cooperation was the most practiced form of inter-professional collaboration, next to it is partnership. The study revealed a significant relationship between inter-professional collaboration and knowledge management practices. It shows that only cooperation significantly influenced knowledge management practices while knowledge capturing and knowledge dissemination significantly influenced inter-professional collaboration. The study concluded that Federal Tertiary Hospitals in Nigeria will perform better if they can sustain the culture of knowledge management practices and inter-professional collaboration.