The clonality and mechanisms of macrolide resistance were studied among 345 macrolide resistant Streptococcus pneumoniae strains isolated from 24 countries. The mechanisms of macrolide resistance, serotypes and PFGE types of the strains were determined and representative strains of clones from each country were typed by MLST. Among strains tested 215 had the erm(B) gene, 92 the mef(A) gene, 14 had both erm(B) and mef(A), and 24 had alterations in ribosomal proteins [2 with A2059G substitutions in 23S rRNA, 21 with 69GTG71 to TPS change in L4, and one with erm(B) and deletion of leucine at position 68 in L22]. Serogroups 19, 6, and 23, and serotype 14 were the most common serotypes / serogroups. Dissemination of variants of sequence type (ST) 315 and ST156 were observed in Eastern and Central European countries. In Asiatic countries the most common sequence types were variants of ST236 among strains with mef(A) and ST180 among strains with erm(B). Strains with both erm(B) and mef(A) from Mexico and Singapore were variants of ST236. The widespread clone from Slovakia with ribosomal protein L4 mutation was a variant of ST226. Common clones were observed between Europe, Asia, and America. Overall, while serotypes / serogroups of macrolide resistant isolates were limited, multiple PFGE and MLST types were found, with clustering of common clones within countries.