Misuse of antibiotics can provoke increased bacterial resistance. There are no immediate prospects of any new broad-spectrum antibiotics, especially any with activity against enterobacteria, coming onto the market. Therefore, programmes should be implemented to optimise antimicrobial therapy. In a quasi-experimental study, the results for the pre-intervention year were compared with those for the 3 years following the application of an antimicrobial stewardship programme. We describe 862 interventions carried out as part of the stewardship programme at the Hospital Costa del Sol from 2009 to 2011. We examined the compliance of the empirical antimicrobial treatment with the programme recommendations and the treatment optimisation achieved by reducing the antibiotic spectrum and adjusting the dose, dosing interval and duration of treatment. In addition, we analysed the evolution of the sensitivity profile of the principal microorganisms and the financial savings achieved. 93 % of the treatment recommendations were accepted. The treatment actions taken were to corroborate the empirical treatment (46 % in 2009 and 31 % in 2011) and to reduce the antimicrobial spectrum taking into account the antibiogram results (37 % in 2009 and 58 % in 2011). The main drugs assessed were imipenem/meropenem, used in 38.6 % of the cases, and cefepime (20.1 %). The sensitivity profile of imipenem against Pseudomonas aeruginosa increased by 10 % in 2011. Savings in annual drug spending (direct costs) of 30,000 Euros were obtained. Stewardship programmes are useful tools for optimising antimicrobial therapy. They may contribute to preventing increased bacterial resistance and to reducing the long-term financial cost of antibiotic treatment.