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Summary Background Influenza vaccination of healthcare workers (HCWs) is essential for patient safety, their own safety, and hospital operation. However, despite its strong recommendation, studies indicates a low rate of vaccine uptake. Aim To assess rates of, and factors affecting, influenza vaccine uptake among HCWs. Methods A cross-sectional survey was carried out during October 1 st to 16 th , 2015, among HCWs in King Abdullah Medical City in Makkah, Saudi Arabia. A self-administered, anonymous questionnaire was distributed to HCWs; this included questions on demographic characteristics, vaccine uptake, and knowledge, beliefs, attitude, and concern about influenza vaccine. Findings Out of 500 HCWs approached, 447 returned valid self-reported questionnaires with response rate 89.4%. Overall, 88.3% of the participants reported receiving vaccination during the 2014/15 season, higher than during the 2013/14 (61.2%) and 2012/13 (54.5%) seasons. Self-protection (81.5%) was the main reason for vaccination, whereas 73.4% of HCWs reported vaccination to protect patients. The main reasons for vaccination avoidance were misconception that the vaccine causes influenza (38.5%) and concern about vaccine efficacy (32.7%). Logistic regression analysis revealed that the following were independently associated with vaccine receipt among HCWs: awareness of vaccine guidelines; intention to receive the vaccine next season; nurses and other HCWs compared to physicians; longer practice; and age >40 years. Conclusion A good uptake of influenza vaccine was achieved during the 2014/15 season following adoption of mandatory vaccination policy. Awareness programmes are needed to correct HCWs' misconceptions about the vaccine. Efforts need to focus especially on physicians, younger staff and new recruits.