Objectives To develop near-infrared spectroscopic (NIRS) quantitative models for the assay of ciprofloxacin in proprietary and generic ciprofloxacin 500 mg intact and powdered tablets. Methods Ciprofloxacin 500 mg tablets were pruchased from the UK and the Tanzanianmarkets. Tablets in both intact and powdered forms were utilized to construct calibration models. Tablets of a single proprietary brand (Bayer, 500 mg)were powdered and diluted with excipient(s) to give mixtures of different concentrations of ciprofloxacin. In addition, standard additions of ciprofloxacin FOSS NIRSystem 6500 NIR spectrometer using a rapid content analyser. Each spectrum was the sum of 32 scans over the wavelength range 1100-2500 nm at 2 nm interval. Four spectra were also recorded from each tablet, two on each side at 90 degrees to each other. Four spectra were also recorded from the powdered samples in Waters (4 mm) vials shaking between measurements. The average of the spectra was taken in both cases in standard normal variate second derivative (SNV-D2) form. Results The ciprofloxacin tablets had a range of activity between 55 and 77% m/m estimated as the ratio of the label claim (in milligrams) to the weight of the tablet. These data were used to construct the Intact Tablet Model. The powdered models used various ranges of ciprofloxacin between 0 and 100%. In all cases, a partial least squares regression (PLSR) algorithm (Unscrambler 7.5) was utilized. The spectra were split into calibration and validation sets based on PCA data to give the greatest variability in the calibration set. The ratio of the calibration to validation sets was 75%:25%. Specific partial least squares components were chosen for each model to give the lowest root mean standard error of prediction as a percentage of the label claim (RSEP %). The PLSR loadings showed good correlation with the ciprofloxacin tablet spectrum. The predictive ability of the model was validated against known proprietary and generic intact and powdered tablets. The tablets contained ciprofloxacin or other antibiotics of different classes. A good prediction gave the label claim within +-10% of the ciprofloxacin tablets and 0% for the other tablets. In this respect, the best model that fulfilled the stated criteria was the one which utilized the standard addition of the ciprofloxacin to the crushed Bayer tablets. It gave an r2 value of 0.9989 and RSEP% of 0.96%. In addition, it was able to prdict both ciprofloxacin and blank tablets. Conclusions The NIRS method with PLSR regression is a simple, rapid, non-destructive technique for the determination of cirofloxacin in jkproprietary and generic tablets. It can be used without the need for a reference analytical technique and with an RSEP% as low a 0.96%.