This work summarized the results obtained in an institutional Klebsiella pneumoniae surveillance program recently implemented in Cuba. Eighteen hospitals from five regions provided a total of 228 K. pneumoniae isolates (164 from admitted patients, four from hospital environmental sources, and 60 isolates from community patients). The genetic relationship was assessed by pulsed-field gel electrophoresis and multilocus sequence typing. Antimicrobial susceptibility was determined by the agar dilution method, and bla(ESBL) genes were sequenced. Fifty four K. pneumoniae isolates were extended-spectrum β-lactamases (ESBL)-producers (23.6%), mostly due to the CTX-M-15 enzyme (79.6%). ESBL isolates were grouped in 27 different sequence types (STs), being the most prevalent ST15 (15%), ST152 (13%), and both ST48 and ST147 (11%, respectively). Community-acquired criteria could be demonstrated in 60 patients (26%) corresponding to urological (33%), wound (27%), respiratory (27%), and otic (13%) infections. Population structure analysis showed that our isolates corresponded to a highly polyclonal population with 10 nonpreviously described STs, demonstrating the importance of local epidemiological studies. We report the first data of the population structure of ESBL-producing K. pneumoniae isolates obtained in a national multicenter surveillance Cuban program. Results showed that a highly polyclonal ESBL-producer K. pneumoniae population was mainly due to CTX-M-15 carriage, whereas carbapenemases production was not present.