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Introduction: Working with cleaning products is associated with occupational contact dermatitis in health workers (HWs), but information on predictors for these outcomes is limited. Objectives: This study investigated the prevalence of work‐related skin symptoms (WRSS) and associated factors in HWs exposed to cleaning agents in two Southern African tertiary hospitals. Methods: A cross‐sectional study of 697 HWs used an interviewer‐administered questionnaire and assessed for atopy using Phadiatop. Results: HWs' median age was 42 years, 77.0% were female and 42.5% were atopic. The prevalence of WRSS in the last 12 months was 14.8%, 12.3% had probable contact dermatitis (PCD) and 3.2% had probable contact urticaria (PCU). Technicians (ORadj 3.91) and tasks involving cleaning and disinfection of skin wounds (ORadj 1.98) were associated with WRSS in the past year. Factors associated with PCD included sterilizing instruments, disinfecting skin before procedures and use of wound adhesives. Factors associated with PCU included specimen preparation using formalin, medical instrument sterilization tasks, and skin/wound cleaning and disinfection. Appropriate glove use when performing patients' skin/wound care was protective against WRSS. Conclusions: Tasks involving cleaning and disinfecting patients' skin and wounds were associated with WRSS in HWs, especially when performed without gloves. [ABSTRACT FROM AUTHOR]