The National Aeronautics and Space Administration (NASA) Nature Run (NR), released for use in Observing System Simulation Experiments (OSSEs), is a 2-year long global non-hydrostatic free-running simulation at a horizontal resolution of 7 km, forced by observed sea-surface temperatures (SSTs) and sea ice, and inclusive of interactive aerosols and trace gases. This article evaluates the NR with respect to tropical cyclone (TC) activity. It is emphasized that to serve as a NR, a long-term simulation must be able to produce realistic TCs, which arise out of realistic large-scale forcings. The presence in the NR of the realistic, relevant dynamical features over the African Monsoon region and the tropical Atlantic is confirmed, along with realistic African Easterly Wave activity. The NR Atlantic TC seasons, produced with 2005 and 2006 SSTs, show interannual variability consistent with observations, with much stronger activity in 2005. An investigation of TC activity over all the other basins (eastern and western North Pacific, North and South Indian Ocean, and Australian region), together with relevant elements of the atmospheric circulation, such as, for example, the Somali Jet and westerly bursts, reveals that the model captures the fundamental aspects of TC seasons in every basin, producing realistic number of TCs with realistic tracks, life spans and structures. This confirms that the NASA NR is a very suitable tool for OSSEs targeting TCs and represents an improvement with respect to previous long simulations that have served the global atmospheric OSSE community.