This multidisciplinary study evaluates the structural and hydrogeologic evolution of Cretaceous-age reservoirs in the Putumayo basin, Colombia. We focused on the Eastern Cordillera fold-thrust belt along the southern Garzón Massif. Many important hydrocarbon accumulations occurred regionally along the proximal foreland basin and frontal fold-thrust belt defining the eastern margin of the northern Andes. To understand why recent Putumayo basin and adjacent thrust belt exploration has resulted in a wide range of oil quality and limited economic discoveries, we reconstructed the structural evolution, timing of oil migration, and timing of groundwater infiltration by (1) assessing regional trends in formation water, oil, and reservoir properties; (2) quantifying the timing of hydrocarbon generation and migration relative to trap formation using (a) two-dimensional (2-D) and three-dimensional seismic data to define and constrain a restorable balanced cross section from the Upper Magdalena Valley to the Putumayo foreland and (b) coupled one-dimensional thermal basin modeling; (3) evaluating the potential roles of Mesozoic extensional faulting and Paleogene shortening in the generation and preservation of structural traps; and (4) assessing groundwater influx from the modern foothills into the reservoir using a 2-D numerical groundwater flow model. We suggest that four-way closure is limited in the study area, where most foreland-verging structures create three-way fault closures that do not effectively trap light hydrocarbons. In addition, east-dipping structures and a relatively large reservoir outcrop area provide water infiltration pathways. Groundwater modeling suggests reservoirs were water washed by 2–200 million pore volumes since Andean uplift. Finally, average reservoir temperatures are <80°C (<176°F), which further facilitated biodegradation.