Sister chromatid exchange (SCE) can be used to identify early occupational health status in health care workers. Our aim is to comprehensively assess the relationship between long-term exposure to antineoplastic drugs (ADs) and SCE in health care workers via meta-analysis.Five databases were systematically searched for relevant articles published from inception to November 30, 2022. Literature data are expressed as mean difference and 95% confidence intervals (CI) or relative risk and 95% CI. For I2 > 50% trials, random effect model is used for statistical analysis, otherwise fixed effect model is used. This review was registered in the International Prospective Register of Systematic Reviews (identifier CRD42023399914).Fourteen studies were included in this study. Results showed the level of SCE in healthcare workers exposed to ADs was significantly higher than in controls. The mean difference of the SCE trial was 0.53 (95% CI: 0.10-0.95, P = .01) under a random-effects model.The findings suggested a significant correlation between occupational exposure to ADs in health care workers and SCE, requiring the attention of health care workers in general.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.