The response of a deep-water megafaunal assemblage to sedimentation disturbance from hydrocarbon drilling was investigated using remotely operated vehicle video off the Atlantic coast of Venezuela. This was the first assessment of megafauna in bathyal waters in this region. A two-way analysis of variance (ANOVA) design was used to assess patterns in density and assemblage structure both temporally, before and after the drilling event, and spatially, at different distances from the disturbance. High levels of sedimentation occurred within a radius of 20 to 50 m from the drilling site. Megafaunal densities were reduced with high levels of disturbance (from 0.60 m−2 to 0.17 m−2 <20 m from the drilling site). The responses of motile and sessile fauna were different. Sessile fauna were most common (77% total) and reflected trends for total density. Motile megafaunal density was generally higher after drilling (up to double the pre-drill density). Species richness was reduced by disturbance and proximity to the disturbance. Multivariate ANOVA revealed significant differences in assemblage composition with distance and before and after drilling but no interaction. This was most likely a result of variable species-specific responses to disturbance. Megafaunal densities were generally much higher than reported densities from comparable depths in the Gulf of Mexico or from deeper locations in the Caribbean Sea. The responses to sedimentation disturbance were generally less obvious than observed elsewhere and may result from the fauna being adapted to the naturally high levels of sedimentation deriving from the Orinoco River.