BACKGROUND In the present era of automation, the quality of laboratory specimens is critical towards the delivery of accurate and useful results. The mode of collection of the sample is one such variable. Proper collection and handling of blood samples prevent erroneous results, reduce turnaround time and ensure safety of healthcare workers and patients. The study purpose is to compare open and closed systems of blood collection and the impact of closed collection system in the reduction of pre analytical errors and promoting health care worker safety. METHODS This is a prospective comparative study and it was conducted on blood samples collected in the Outpatient Department of Government Medical College, Kottayam and preanalytical study variables were assessed at Departments of Haematology and Biochemistry. At the beginning of the study, the quality and the quantity of specimen, result accuracies and healthcare safety parameters were assessed for 4778 samples using open blood collection system. This was followed by training of the phlebotomists for closed system of blood collection. The same parameters were studied for another 2508 blood samples collected via closed collection system by the same phlebotomists. The open blood collection system was carried out using non vacuum tubes (Plain and K3 EDTA), 5 ml syringe and 23G needles and closed blood collection system used BD vacutainer (K2 EDTA and serum gel tubes), Eclipse TM safety 22G needles and pronto TM reusable safety holders. The study was conducted from 01-01-2021 to 31-03-2021. RESULTS The specimen quality errors namely fibrin mass, strands, haemolysis, recentrifugation, and insufficient volume in biochemistry lab were significantly reduced with introduction of closed collection system. In haematology lab, closed collection system reduced incidence of clotted sample, insufficient volume accompanied by significant reduction in platelet and WBC differential flags. Closed collection system also reduced occurrence of blood smeared containers and blood spillage on test requisition forms, hence improving safety of health care personnel. CONCLUSIONS The study establishes a significant reduction in pre-analytical errors with closed blood collection system, prevents test cancellation and improved workflow efficiency. KEY WORDS Accuracy, Blood Collection Systems, Errors, Phlebotomist, Preanalytical, Spillage, Variables.