Doxycycline is a second-generation semi-synthetic antimicrobial of tetracyclines family. It is a broad spectrum antimicrobial agent used in several countries for the treatment of diseases such as chronic prostatitis, sinusitis, syphilis, chlamydia, pelvic inflammatory disease as well as additives in animal feed to improve its growth. Doxycycline is distributed free of charge through Unified Health System in Brazil, which, according to its acquisition, for subsequent distribution, does not always guarantee the same brand. Five different brands of doxycycline tablets (the reference pharmaceutical of doxycycline, two generic and two similar products) were used for evaluation of the interchangeability of the tablets by determination of average weight, hardness, friability, disintegration, the active principle content, content uniformity and in vitro dissolution. All tablets submitted to the tests of average weight, friability, hardness, and disintegration were according to specification. Tests of content uniformity show drugs out of specification, with contents higher than 105%. In the trial of dissolution, there were no statistical differences in the profiles. Due to the results obtained, all doxycycline tablets analyzed should not be approved by the Quality Control authorities. Sectors of production, analytical development, and quality control should meet to resolve this issue. Thus, the importance of a pharmaceutical equivalence study is important to guarantee a safe interchangeability and consequently the same therapeutic effect.