Introduction: Central Venous Catheters (CVCs) are used for monitoring and managing critically-ill patients. However, their use can lead to serious infectious complications, resulting in significant morbidity, additional medical costs and mortality. Aim: To analyse the causative pathogens and the associated risk factors involved in the causation of central line-related infections and their outcomes. Materials and Methods: This prospective cohort study was conducted among 66 patients admitted to the 10-bed Respiratory Intensive Care Unit (RICU) at the Department of Pulmonary Medicine, SCB Medical College and Hospital, a tertiary-care teaching hospital in Cuttack, Odisha, India, from March 2021 to October 2022, who required central line placement for 48 hours or more. These patients were followed daily and upon the development of new-onset sepsis after 48 hours, two blood samples were collected from both central and peripheral sites for culture and antibiotic susceptibility testing, after excluding other sources of infections. Results: The mean age of patients with CLABSI was 62.85±14.95 years, with the most commonly affected age group being 55-74 years. Total of 66 patients had CVCs in place for more than 48 hours, resulting in 664 catheter days. The overall rate of Central Line Associated Bloodstream Infection (CLABSI) was 30.12 per 1,000 catheter days. The risk factors significantly associated with the development of CLABSI were diabetes mellitus, duration of hospitalisation, APACHE score, length of ICU stay and days of catheter in-situ. However, multivariate analysis revealed that only the length of Intensive Care Unit (ICU) stay (p=0.003) and the presence of diabetes (p=0.012) were independent predictors of acquiring CLABSI. The most common pathogens isolated were Acinetobacter (30%), followed by Enterococcus (25%), Staphylococcus aureus (20%), Methicillin-resistant Staphylococcus Aureus (MRSA) (10%), Pseudomonas (10%) and Coagulase-Negative Staphylococcus (CoNS) (5%). All Gram-positive and Gram-negative pathogens showed 100% sensitivity to linezolid, teicoplanin, vancomycin and polymyxin B, as well as tigecycline, respectively. The remaining strains were Multidrug Resistant (MDR). The overall mortality rate was 66.7%, with CLABSI-associated mortality at 60%. Conclusion: The incidence of CLABSI was high, with significant risk factors significantly associated were prolonged duration of catheterisation, length of hospital and ICU stays, Acute Physiology and Chronic Health Evaluation (APACHE) II score and diabetes mellitus. Gram-positive bacteria predominated, followed by Gram-negative bacteria, with a significant proportion of MDR organisms.