During the containment phase of the 2009 influenza A(H1N1) pandemic, mass treatment and prophylaxis with oseltamivir was used to control an outbreak of pandemic influenza in a primary school in Sheffield, United Kingdom, where ten cases of pandemic influenza had been laboratory confirmed over a three day period in June 2009. A subsequent cross-sectional survey showed that 51 of 297 (17%) pupils and 10 of 58 (17%) reported an influenza-like illness. The most common symptoms were headache, cough, fever, tiredness, sore throat and nausea. Fifty-three staff and 273 pupils took oseltamivir for treatment or prophylaxis. Of this group, 41% (113/273) of pupils and 47% (25/53) of staff reported adverse effects. Overall, 14% (37/273) of pupils and 20% (11/53) of staff did not complete the course of oseltamivir, primarily due to adverse effects. Nausea, vomiting and rash were statistically significantly associated with failing to complete the course of oseltamivir. Given the potential for side effects from oseltamivir, particularly among those without influenza who receive the drug for prophylaxis, our findings have two important implications. Firstly, the benefits of mass treatment in an outbreak setting must clearly be greater than the benefits of targeted treatment. Secondly, any large scale regional or state level system for distribution of antiviral drugs for treatment should ideally include a robust quantification of an individual’s probability of infection with influenza virus in order to avoid unnecessary treatment.