The discovery of three new species of Synophis snakes from the eastern slopes of the tropical Andes in Ecuador and Peru is reported. All previous records of S. bicolor from eastern Ecuador correspond to S. bogerti sp. n., which occurs between 1000–1750 m along a large part of the Amazonian slopes of the Ecuadorian Andes. In contrast, Synophis zamora sp. n. is restricted to southeastern Ecuador, including Cordillera del Cóndor, between 1543–1843 m. Synophis insulomontanus sp. n. is from the eastern slopes of the Andes in central and northern Peru, between 1122–1798 m, and represents the first record of Synophis from this country. All three new species share in common a large lateral spine at the base of the hemipenial body. A molecular phylogenetic tree based on three mitochondrial genes is presented, including samples of Diaphorolepis wagneri. Our tree strongly supports Synophis and Diaphorolepis as sister taxa, as well as monophyly of the three new species described here and S. calamitus. Inclusion of Synophis and Diaphorolepis within Dipsadinae as sister to a clade containing Imantodes, Dipsas, Ninia, Hypsiglena and Pseudoleptodeira is also supported.