A six-year retrospective study was undertaken to examine the effect of the recent penicillin G (penG) shortage on antibiotic prescribing practices at a tertiary care centre in the US. Prior to the shortage, penG was predominantly used for intrapartum prophylaxis of group B streptococcal disease. As the supply of penG ended temporarily in October 1999, penG use declined dramatically, ampicillin replaced penG in obstetrics and a shift to broad-spectrum agents was noted in non-obstetric patients potentially eligible for penG treatment. Shortage-triggered treatment changes had a negative effect on prescribing patterns, which may contribute to antibiotic resistance.