Ciprofloxacin is a fluoroquinolone antibiotic employed to treat infections. There are over three hundred registered generic brands of ciprofloxacin in Nigeria. There has been an observed marked variation in therapeutic or clinical outcome with change in brands by health professionals and patients. In a previous study of six (6) brands we had reported a high degree of inequivalence. In this study, twenty-nine (29) brands of ciprofloxacin were extensively evaluated against compendia requirements. Microbial sensitivity against two test organisms was conducted. In-vitro drug release and in-vivo simulation were established. Analysis of the data generated indicated that all brands passed qualitative test using TLC and disintegration test, six failed hardness test, one failed friability, nine failed antimicrobial assay and six failed percentage content assay. Conclusions drawn from the study for evidence-based clinical decisionwould include the fact that three brands only were found to be bioequivalent to the innovator brand, Ciproxin; while eight brands were bio-inequivalent using the three models of similarity factor (f2), and difference factor (f1) in two media and dissolution efficiency (DE) in pH 4.5. The three brands (Cipro-All, Cifran And Ciprogem) may confidently be used interchangeably with the innovator brand Keywords: Bioequivalence; Ciprofloxacin Drug quality; Generic substitution; Post-marketing surveillance