Chemical products such as PEO/PPO block copolymers or alkoxylated resins tend to work well in chemical demulsification of light hydrocarbons (degrees API > 20) but fail to do so in the presence of heavy and extra heavy crude emulsions. Moreover, a large knowledge gap between the relationship of instability mechanisms at the liquid-liquid interface and the tendency of demulsifier systems to promote phase separation has limited the ability of practitioners in field operations to properly select a system for a particular application. To address this issue, here, an enhanced quantitative protocol is put forward to assess the chemical demulsification of heavy crude oil (HCO) emulsions by coupling transmission/backscattering measurements to traditional bottle tests. The applicability of the method was evaluated by adding a wide variety of commercially available demulsifiers to HCO emulsions from a Colombian oilfield. The collected data on interfacial tension and average droplet size showed that for the complex case of HCO emulsions, interfacial activity and fast kinetics are not sufficient criteria for phase separation. The best performing chemicals (separated water -85%) exhibited a low reduction of the interfacial tension at equilibrium (IFT similar to 20 mN/m). This evidence strongly suggests that separation might be likely triggered after the intermingling of the demulsifier with the oil phase such that the density difference between phases is considerably increased (similar to 5% change on average). Furthermore, HPLC-MS results showed that spatial and chemical configuration, as well as steric effects, drive the performance of demulsifiers and must be carefully considered for new developments.