We assess the volcanic hazard derived from pyroclastic density currents (PDCs) at Tungurahua volcano, Ecuador, using a probabilistic approach based on the analysis of calibrated numerical simulations. We address the expected variability of explosive eruptions at Tungurahua volcano by adopting a scenario-based strategy, where we consider three cases: small magnitude violent Strombolian to Vulcanian eruption (VEI 2), intermediate magnitude sub-Plinian eruption (VEI 3), and large magnitude sub-Plinian to Plinian eruption (VEI 4–5). PDCs are modeled using the branching energy cone model and the branching box model, considering reproducible calibration procedures based on the geological record of Tungurahua volcano. The use of different calibration procedures and reference PDC deposits allows us to define uncertainty ranges for the inundation probability of each scenario. Numerical results indicate that PDCs at Tungurahua volcano propagate preferentially toward W and NW, where a series of catchment ravines can be recognized. Two additional valleys of channelization are observed in the N and NE flanks of the volcano, which may affect the city of Baños. The mean inundation probability calculated for Baños is small (6 ± 3%) for PDCs similar to those emplaced during the VEI 2 eruptions of July 2006, February 2008, May 2010, July 2013, February 2014 and February 2016, and on the order of 13 ± 4% for a PDC similar to that produced during the sub-Plinian phase of the August 2006 eruption (VEI 3). The highest energy scenario (VEI 4–5), for which we present and implement a novel calibration procedure based on a few control points, produces inundation areas that nearly always include inhabited centers such as Baños, Puela and Cotaló, among others. This calibration method is well suited for eruptive scenarios that lack detailed field information, and could be replicated for poorly-known active volcanoes around the world.