Introduction: Fine needle aspiration (FNA) is recognized worldwide as the primary diagnostic method for evaluating thyroid nodules. Samples collected by FNA can be spread directly onto slides, prepared for cell blocks, or processed as liquid-based cytology. Advocates of the traditional smear technique emphasize that background material such as colloid, cell sequencing characteristics in cell clusters, and cellularity is important in cytological diagnosis. They state that these properties are not observed in liquid-based liquids. Liquid-based cytology techniques aim to provide standardized slides of homogeneous cellular smears with well-preserved cell morphology, producing more precise visualization, shorter interpretation time, and more reproducible results. This study aimed to investigate and compare the diagnostic performance of liquid-based thyroid FNA samples prepared with SurePath and Cytospin over the last 6 years. Methods: Patients who underwent ultrasound-guided FNA between January 2015 and December 2021 were included in the study. Cytology reports, pathology reports, and demographic information of the patients were collected from the Hospital Information Management System. The programs “SPSS for Windows 21” and “MedCalc Diagnostic Test Evaluation Calculator” were used for data analysis. Chi-square tests were used in crosstab analysis. The Kolmogorov-Smirnov two-sample test, two proportions test, and the confidence interval tests were used to analyze the variables of the methods. P < .05 was considered statistically significant. Results: The study population comprised 4,855 patients, 83.8% female and 16.2% male. There were no statistical differences in age and gender distribution in the population of both methods. Nondiagnostic outcome rates were 11.2% for SurePath and 12.8% for Cytospin. Sensitivity, specificity, and accuracy values for SurePath and Cytospin methods were determined as 58.57%, 98.28%, and 91.12% and 79.07%, 96.88%, and 94.03%, respectively. Conclusion: In our study, although the qualitative analytical results were slightly in favor of the cytospin method, we think both ways can be used safely, especially in hospitals where the clinics performing sampling activities are variable and many, as well as in pathology laboratories where the workload is intense.