BackgroundThe MC‐80 (Mindray, Shenzhen, China), a newly available artificial intelligence (AI)‐based digital morphology analyzer, is the focus of this study. We aim to compare the leukocyte differential performance of the Mindray MC‐80 with that of the Sysmex DI‐60 and the gold standard, manual microscopy.MethodsA total of 100 abnormal peripheral blood (PB) smears were compared across the MC‐80, DI‐60, and manual microscopy. Sensitivity, specificity, predictive value, and efficiency were calculated according to the Clinical and Laboratory Standards Institute (CLSI) EP12‐A2 guidelines. Comparisons were made using Bland–Altman analysis and Passing‐Bablok regression analysis. Additionally, within‐run imprecision was evaluated using five samples, each with varying percentages of mature leukocytes and blasts, in accordance with CLSI EP05‐A3 guidelines.ResultsThe within‐run coefficient of variation (%CV) of the MC‐80 for most cell classes in the five samples was lower than that of the DI‐60. Sensitivities for the MC‐80 ranged from 98.2% for nucleated red blood cells (NRBC) to 28.6% for reactive lymphocytes. The DI‐60's sensitivities varied between 100% for basophils and reactive lymphocytes, and 11.1% for metamyelocytes. Both analyzers demonstrated high specificity, negative predictive value, and efficiency, with over 90% for most cell classes. However, the DI‐60 showed relatively lower specificity for lymphocytes (73.2%) and lower efficiency for blasts and lymphocytes (80.1% and 78.6%, respectively) compared with the MC‐80. Bland–Altman analysis indicated that the absolute mean differences (%) ranged from 0.01 to 4.57 in MC‐80 versus manual differential and 0.01 to 3.39 in DI‐60 versus manual differential. After verification by technicians, both analyzers exhibited a very high correlation (r = 0.90–1.00) with the manual differential results in neutrophils, lymphocytes, and blasts.ConclusionsThe Mindray MC‐80 demonstrated good performance for leukocyte differential in PB smears, notably exhibiting higher sensitivity for blasts identification than the DI‐60.