BackgroundBest practice of infection prevention and control (IPC) is a hallmark for the patient care in health care settings, but it is a major problem in developing countries like Ethiopia where resources are limited. Ethiopia Federal Ministry of Health working to strengthen its IPC program, but still it there is no organized study conducted on assessment of performance gaps and implementation challenges of IPC practice faced by hospital staffs particularly among sanitary workers (SWs) at public hospitals inline to national and international guidelines.AimThis study focuses on compliance and determinants of IPC among sanitary worker in public hospitals in eastern Ethiopia: A cross sectional study design.MethodA cross‐sectional study was conducted among 809 SWs and eight IPC experts in public hospitals, eastern Ethiopia, from May to August 2023. A standard questionnaire was used to collect data. Face‐to‐face interview was conducted. Ten (10) question pursued to answer YES/NO were prepared. The cut point for categories of IPC practice was 1: Good (16–20 scores), 2: Fair (10–15 scores), and 3: Poor (<10 scores). The cut point for compliance and noncompliance of IPC practice among hospitals was mean (500.1). Multi‐level ordinal logistic regression models was applied to explore the association of dependent and independent variables at individual level (Model 1), hospital level (Model 2) and at both (Model 3). Crude odds ratio (COR) and adjusted odds ratio (AOR) at 95% confidence interval (CI) were used to report the result.ResultThe compliance of IPC practice among SWs was 36.21% (32.72, 39.82%). The Multilevel ordinal logistic regression model shows that SWs who have good knowledge of IPC trend (AOR: 4.70, 95% CI: 2.11–10.46), SWs who are not addictive with alcohol (AOR: 2.35, 95% CI: 1.15,4.78) and chew Khat (AOR: 1.62, 95% CI: 1.06,2.46) and smoke cigarette (AOR: 3.15, 95% CI: 2.35–5.41), and SWs without job stress (AOR: 1.46, 95% CI: 0.86–2.48) were more compliant to IPC practice. Similarly, those who do not have workload (AOR: 2.74, 95% CI: 1.56–4.82), work <8 h/day (AOR: 1.46, 95% CI: 0.92–2.30), and those who have good social recognition in hospitals (AOR: 6.08, 95% CI: 4.24–8.71) were more likely to increase the compliance of IPC practice among SWs. The multilevel random‐effect model revealed 93.71% of the variability of compliance of IPC practice explained by both individual and hospital level factors.ConclusionThe overall study found that inadequate IPC practice was reported among SWs as well as by IPC experts due to poor knowledge of IPC trend and individual behaviors and working environment. Thus, the study advised that hospitals have to develop and establish IPC implementation guidelines in order to solve the concerns among these groups; national IPC office should follow its implementation across health care settings particularly at public hospitals.