Abstract Background and Aims Even though vegetation size in infective endocarditis (IE) has been associated with embolic events (EEs) and mortality risk, it is unclear whether vegetation size associated with these potential outcomes is different in left-sided IE (LSIE). This study aimed to seek assessing the vegetation cut-off size as predictor of EE or 30-day mortality for LSIE and to determine risk predictors of these outcomes. Methods The European Society of Cardiology EURObservational Research Programme European Infective Endocarditis is a prospective, multicentre registry including patients with definite or possible IE throughout 2016–18. Cox multivariable logistic regression analysis was performed to assess variables associated with EE or 30-day mortality. Results There were 2171 patients with LSIE (women 31.5%). Among these affected patients, 459 (21.1%) had a new EE or died in 30 days. The cut-off value of vegetation size for predicting EEs or 30-day mortality was >10 mm [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.13–1.69, P = .0015]. Other adjusted predictors of risk of EE or death were as follows: EE on admission (HR 1.89, 95% CI 1.54–2.33, P < .0001), history of heart failure (HR 1.53, 95% CI 1.21–1.93, P = .0004), creatinine >2 mg/dL (HR 1.59, 95% CI 1.25–2.03, P = .0002), Staphylococcus aureus (HR 1.36, 95% CI 1.08–1.70, P = .008), congestive heart failure (HR 1.40, 95% CI 1.12–1.75, P = .003), presence of haemorrhagic stroke (HR 4.57, 95% CI 3.08–6.79, P < .0001), alcohol abuse (HR 1.45, 95% CI 1.04–2.03, P = .03), presence of cardiogenic shock (HR 2.07, 95% CI 1.29–3.34, P = .003), and not performing left surgery (HR 1.30 95% CI 1.05–1.61, P = .016) (C-statistic = .68). Conclusions Prognosis after LSIE is determined by multiple factors, including vegetation size.