New records of 15 Lepraria species from South America are presented. Two species are newly described from the Bolivian Andes: Lepraria achariana Flakus & Kukwa (major compounds: lecanoric, angardianic/roccellic acids and anthraquinones) and L. neojackii Flakus & Kukwa (major compounds: porphyrilic, angardianic/roccellic, cf. rangiformic acids and anthraquinone). Lepraria impossibilis, L. lecanorica and L. rigidula are reported as new for the Southern Hemisphere, L. alpina, L. aff. caesiella and L. squamatica as new to South America, and other species as new to several countries (Argentina, Bolivia, Brazil, Peru, Uruguay). In addition, two putative, undescribed species are discussed. Chemistry, ecology and general information concerning distribution of the species are presented, and the differentiation of some critical taxa discussed. A provisional key to Lepraria in South America is provided.