The COVID-19 pandemic has resulted in excess mortality due to both COVID-19 directly and other conditions, including cardiovascular (CV) disease. We aimed to explore the excess in-hospital mortality, unrelated to COVID-19 infection, across a range of CV diseases. A systematic search was performed for studies investigating in-hospital mortality among patients admitted with CV disease without SARS-CoV-2 infection compared with a period outside the COVID-19 pandemic. Fifteen studies on 27 421 patients with CV disease were included in the analysis. The average in-hospital mortality rate was 10.4% (n = 974) in the COVID-19 group and 5.7% (n = 1026) in the comparator group. Compared with periods outside the COVID-19 pandemic, the pooled risk ratio (RR) demonstrated increased in-hospital mortality by 62% during COVID-19 [95% confidence interval (CI) 1.20-2.20, P = 0.002]. Studies with a decline in admission rate >50% during the COVID-19 pandemic observed the greatest increase in mortality compared with those with <50% reduction [RR 2.74 (95% CI 2.43-3.10) vs. 1.21 (95% CI 1.07-1.37), P < 0.001]. The observed increased mortality was consistent across different CV conditions (P = 0.74 for interaction). In-hospital mortality among patients admitted with CV diseases was increased relative to periods outside the pandemic, independent of co-infection with COVID-19. This effect was larger in studies with the biggest decline in admission rates, suggesting a sicker cohort of patients in this period. However, studies were generally poorly conducted, and there is a need for further well-designed studies to establish the full extent of mortality not directly related to COVID-19 infection. © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.