The moisture content of vegetation canopies controls various ecosystem processes such as plant productivity, transpiration, mortality, and flammability. Leaf moisture content (here defined as the ratio of leaf water mass to leaf dry biomass, or live-fuel moisture content, LFMC) is a vegetation property that is frequently used to estimate flammability and the danger of fire occurrence and spread, and is widely measured at field sites around the globe. LFMC can be retrieved from satellite observations in the visible and infrared domain of the electromagnetic spectrum, which is however hampered by frequent cloud cover or low sun elevation angles. As an alternative, vegetation water content can be estimated from satellite observations in the microwave domain. For example, studies at local and regional scales have demonstrated the link between LFMC and vegetation optical depth (VOD) from passive microwave satellite observations. VOD describes the attenuation of microwaves in the vegetation layer. However, neither were the relations between VOD and LFMC investigated at large or global scales nor has VOD been used to estimate LFMC. Here we aim to estimate LFMC from VOD at large scales, i.e. at coarse spatial resolution, globally, and at daily time steps over past decadal timescales. Therefore, our objectives are: (1) to investigate the relation between VOD from different frequencies and LFMC derived from optical sensors and a global database of LFMC site measurements; (2) to test different model structures to estimate LFMC from VOD; and (3) to apply the best-performing model to estimate LFMC at global scales. Our results show that VOD is medium to highly correlated with LFMC in areas with medium to high coverage of short vegetation (grasslands, croplands, shrublands). Forested areas show on average weak correlations, but the variability in correlations is high. A logistic regression model that uses VOD and additionally leaf area index as predictor to account for canopy biomass reaches the highest performance in estimating LFMC. Applying this model to global VOD and LAI observations allows estimating LFMC globally over decadal time series at daily temporal sampling. The derived estimates of LFMC can be used to assess large-scale patterns and temporal changes in vegetation water status, drought conditions, and fire dynamics.