BackgroundTelesurgery has become helpful in overcoming the current shortage of surgeons and reducing the barriers to timely and effective surgical intervention caused by long-distance travel, which is caused by distance, cost, complexity and frequent hazards. However, knowledge and attitude remain challenges in the implementation of such a system.ObjectiveThis study aimed to assess physicians’ knowledge and attitude towards telesurgery and associated factors at resource-limited setting, Northwest Ethiopia.Method and analysisA simple random sampling method was carried out to choose study participants from each referral hospital, and data were collected using self-administered questionnaires. Descriptive and inferential statistics were applied to estimate knowledge and attitudes towards telesurgery among physicians and to identify factors associated with physician knowledge and attitudes towards telesurgery.Study designCross-sectional study design.SettingThis study was conducted at six specialised referral hospitals and two specialised and teaching referral hospitals in the Amhara region, northwest Ethiopia.Result408 physicians were included for analysis, with a response rate of 96.45%. Among study participants, 47.8% and 43.1% had good knowledge and attitudes towards telesurgery, respectively. Educational status, digital literacy, source of information, computer training, digital health training and internet access in the organisation were factors associated with a physician’s knowledge of telesurgery. Moreover, physician’s knowledge, technology use, educational status, computer training, computer access and internet access in the organisation were factors associated with physicians’ attitudes towards telesurgery.Conclusion and recommendationAlmost half of physicians had good knowledge, and less than half had a good attitude towards telesurgery, so healthcare policy-makers should improve physicians’ digital literacy, technology use and internet access to enhance their knowledge and attitudes for future implementation.