The breeding success of endangered colonial nesting species is important for their conservation. Many species of Gyps vultures form large breeding colonies that are the foci of conservation efforts. The Cape Vulture is a globally threatened species that is endemic to southern Africa and has seen a major reduction in its population size (≥ 50% over 48 years). There is evidence that breeding colonies are prone to desertion as a result of human disturbance. Factors that influence the occupancy and breeding success of individual nest‐sites is not fully understood for any African vulture species. We investigated cliff characteristics and neighbour requirements of the Msikaba Cape Vulture colony, a major breeding colony in the southern node of the population in the Eastern Cape, South Africa, together with their nest‐site occupation and breeding success over 13 years. In total, 1767 breeding attempts were recorded. Nest‐sites that had a higher elevation, smaller ledge depth, greater total productivity and were surrounded by conspecifics were more likely to be occupied, although the amount of overhang above the nest was not an important predictor of occupancy. In accordance with occupation, nest‐sites with a smaller ledge depth had higher breeding success; however, nests with a greater overhang were also more successful and height of the nest‐site was not an important predictor of breeding success. The breeding success of a nest‐site in a given year was positively influenced by the number of direct nest neighbours, and nests in the middle of high‐density areas had greater breeding success. This suggests that maintaining a high nest density may be an important consideration if declines of reproducing adults continue. Breeding success declined over the study period, highlighting the effects of a temporal variation or observer bias. Our results identified optimal nest‐site locations (ledge depths of 1 m, at a height of 180 m) and their effects on breeding success. This information can be used for planning reintroduction efforts of the endangered Cape Vulture and for their ongoing conservation.