Surgery is an effective therapy in the treatment of left-sided infective endocarditis (IE) in patients for whom antibiotic treatment alone is unlikely to be curative or may be associated with ongoing risk of complications. However, the interplay between indication for surgery, its risk, and timing is complex and there continue to be challenges in defining the effects of surgery on disease-related outcome. Guidelines published by the American College of Cardiology/American Heart Association and the European Society of Cardiology provide recommendations for the use of surgery in IE, but these are limited by a low level of evidence related to predominantly observational studies with inherent selection and survival biases. Evidence to guide the timing of surgery in IE is less robust, and predominantly based on expert consensus. Delays between IE diagnosis and recognition of an IE complication as a surgical indication and transfers to surgical centres also impact surgical timing. This comparison of the two guidelines exposes areas of uncertainty and gaps in current evidence for the use of surgery in IE across different indications, particularly related to its timing and consideration of operative risk.