Merremia macrocalyx is a vine that grows over other plants or as a low creeper and is considered a weed of important crops. Study of its reproductive biology showed that its flowers comprise the typical features of the melittophilous pollination syndrome. Anthophoridae, Apidae, and Halictidae were its main floral visitors. Merremia macrocalyx showed a mixed mating system with features that promote outcrossing while allowing some autogamy. Floral biomass was allocated mainly to the corolla (attraction) which, together with the presence of herkogamy and protandry, favors out-crossing. Nevertheless, it is self-compatible and partially autogamous due to the position of anthers above the stigma. Foraging behavior of pollinators could also facilitate deposition of self pollen on the stigma. Ovule abortion was the main predispersal loss of potential seed production, closely followed by flower and fruit abortion. Predispersal seed predation and seed abortion were relatively low. Specimens of Megacerus flabelliger (Bruchidae) were found emerging from the seeds as well as some wasps belonging to families recognized as parasitoids. The mixed mating system showed by Merremia macroclayx, together with its pollination by generalist bees, provides advantages for its development as a weed.