Abstract Background: In limited resource settings, compliance to proper personal protective equipment (PPE) use is challenging. This study aims to characterize the pattern of PPE use among healthcare workers (HCWs) during the first wave of coronavirus diseases-2019 (COVID-19) in Egypt and to determine the factors associated with compliance to the proper use of PPE. Methods: A cross-sectional study was conducted among Egyptian HCWs using an online self-administered questionnaire. Participants were classified as “Compliant” or “Non-compliant” according to their score. Results: A total of 404 responses were analyzed, with a mean age of 36.6 ± 8.4 years, and 56.4% were females. Non-compliant HCWs represented 53.2% of participants. The majority reported shortage in N95 respirators (91.3%) and practiced extended PPE use (88.1%). Better compliance to proper PPE use was reported: females (51.3%, p = 0.05), Physicians (54.2 %, p = 0.005), medical specialities (34.7 %, p < 0.001), eight hours/day (71.3%, p < 0.001). The significant predictors for compliance were; receiving prior training on the proper use of PPE (OR: 4.59, CI: 2.22–9.47, p ≤ 0.001), exposure to COVID-19 patients (OR: 2.75, CI: 1.19–6.35, p = 0.02) and performing procedures that pose HCWs at a high risk of exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (OR: 2.21, CI: 1.04–4.71, p = 0.04). The high percentage of non-compliant HCWs turns on a warning signal. Increase the availability of PPE, prioritize their use, provide more focus on training of HCWs and monitor their compliance is highly recommended.