To develop and evaluate molecularly imprinted nanocarriers for sustained release of erythromycin in physiological buffer media. Erythromycin-imprinted poly(methacrylic acid-co-trimethylolpropane trimethacrylate) nanocarriers and corresponding control nanocarriers were prepared by free-radical precipitation polymerization. The nanocarriers were characterized by transmission electron microscopy, dynamic light scattering, and nitrogen sorption analysis. Binding studies were carried out with erythromycin and five structurally unrelated drugs. Molecular descriptors of the drugs were computed and correlated to measured binding data by multivariate data analysis. Loading with erythromycin and in vitro release studies were carried out in physiological buffer media. Kinetic models were fitted to drug release data. The template affected the size and morphology of the nanocarriers. Binding isotherms showed that erythromycin-imprinted nanocarriers had a higher erythromycin binding capacity than corresponding control nanocarriers. Multivariate data analysis, correlating binding to molecular descriptors of the drugs, indicated a molecular imprinting effect. Erythromycin loading capacity was 76 mg/g with a loading efficiency of 87%. Release studies in physiological buffer showed an initial burst release of a quarter of loaded erythromycin during the first day and an 82% release after a week. The release was best described by the Korsmeyer-Peppas model. Sustained release of erythromycin in physiological buffer was demonstrated.