This observational study was designed to evaluate the acceptability of oral antibiotics (including generics) commonly prescribed to children by community practitioners in France. Between February and July 2006, the parents of 953 children enrolled by 46 pediatricians completed a questionnaire, including a taste assessment based on representations of five facial expressions. The proportions of "satisfactory" taste judgments showed a significant difference between amoxicillin-clavulanate reference product and its generics (77.9% vs. 65%, p = 0.01). The amoxicillin-clavulanate generics were more likely than the reference product to be spat out at least once (28.7% vs. 19%, p = 0.05). The full treatment course was taken by 91.7% and 82.3% of children prescribed the amoxicillin-clavulanate reference product and its generics, respectively (p = 0.02). The proportions of "satisfactory" taste judgments showed no significant difference between amoxicillin reference product and generics (64.3% vs. 72.5%, p = 0.3). The amoxicillin generics were not different from the reference product to be spat out at least once (8.6% vs. 14.3%, p = 0.2). The full treatment course was taken by 90.7% and 94.6% of children prescribed the amoxicillin reference product and its generics, respectively (p = 0.3). This study suggests the role of the active substance in the taste, and calls for the evaluation of palatability of future drugs (generics and references) before granting of the marketing authorization, particularly for active substances of poor taste; this palatability plays a significant role in the compliance of the treatment, notably in children. Poor compliance increases the risk of therapeutic failures and the emergence of resistance.