Background <p>The number of CD4 T cells is an important indicator of immune status in people living with HIV (PWH). In China, numerous CD4 count instruments have been approved; however, no studies have been conducted to systematically compare the performance of these instruments.</p> Methods <p>We retrospectively analyzed data from the national proficiency testing program for CD4 T-cell counts in China from 2016 to 2023. We conducted comparative analysis to evaluate the performance of 10 mainstream CD4 count instruments. Passing-Bablok regression and mix-effects model analyses were used to analyze the agreement and interchangeability of test results among instruments.</p> Results <p>The proportion of laboratories participating in the CD4 proficiency testing program and using Chinese-manufactured and point-of-care testing instruments has increased annually, from 4.7% to 29.7% and from 3.3% to 8.1%, respectively. The results of the 10 devices tested showed strong correlations and agreement with target values, with correlation coefficients (R²) ranging from 0.952 to 0.983 and with the mean bias ranged from -1 to + 95 cells/µL across the 10 devices. Strong agreement was observed among the results for the 10 instruments, slopes ranged from 0.866 to 1.214, while the intercepts varied from  -42.3 cells/µL to + 24.0 cells/µL. After adjusting for sample and laboratory effects using a linear mixed-effects model, eight instruments (B, C, D, M, J, F_P, L_P, H) produced significantly lower values than the reference instrument A (adjusted mean = 613.0; differences: -92.0 to -20.3; all <i>p</i> &lt; 0.05). Tukey-adjusted pairwise comparisons identified H, L_P, and F_P as a distinct low-value subgroup, although their measurements remained within the acceptable range.</p> Conclusions <p>The performance of commonly used CD4 count instruments was comparable and can meet the needs of HIV testing laboratories.</p> Clinical trial <p>Not applicable.</p>