Aims: To assess the viability of replacing serum samples with plasma samples in various clinical chemistry and immunoassay tests and to examine the implications of turnaround time (TAT) and sample quality during the transition process.Methods: We compared the results of 27 paired clinical chemistry and 13 immunoassay tests from samples obtained using gel separator serum and gel separator lithium heparinized plasma (LIH) tubes. We used regression analysis, bias values, and Bland-Altman plots to compare the performance of serum and LIH tubes in various clinical chemistry and immunoassay tests. We collected and evaluated sample aspiration errors, hemolysis index values, and TAT data from the laboratory information system before and after switching to plasma in our study.Results: Most tests showed no significant difference between the serum and LIH. However, for some analytes, total error (TE) values exceeded the total allowable error (TEa) limits derived from the biological variation database. Notably, insulin TE value did not exceed TEa, but it consumed near all its error budget. Consequently, we determined the alternative allowable error limits for some tests and found that plasma tubes could be used instead of serum tubes for most tests, except for lactate dehydrogenase (LDH). Plasma tubes improved the sample quality, reduced the incidence of aspiration errors, and decreased TAT in the emergency laboratory. We observed significant reductions in TAT after switching to plasma tubes.Conclusion: Our study showed that LIH tubes can replace serum tubes in most clinical chemistry and immunoassay tests. Using LIH tubes in clinical laboratories can improve healthcare quality and reduce the workload of the laboratory staff.