Inappropriate antimicrobial prescribing contributes to the global spread of antimicrobial resistance. The pending weekend with changed availability of general practitioners (GP) and increased patient concern may increase the intention to prescribe antimicrobials. The aim of this study is to analyse variation in antimicrobial prescribing between weekdays and weekend in Irish general practice. All prescribing data over a 15 month period was obtained from the 30 practices participating in the Supporting the Improvement and Management of Prescribing for urinary tract infection (SIMPle) study. Antimicrobials were classified using anatomical therapeutic chemical classification code guidelines. Prescribing of antimicrobials per total number of prescriptions was compared between weekdays (Monday to Thursday) and the weekend (Friday to Sunday). Antimicrobials were generally more often prescribed during weekends; the antimicrobial prescribing rate was greater by 9.2 % on Friday compared to average prescribing on other weekdays (21.4 vs. 19.6 %). The chance of an antimicrobial prescription was 1.07 (95 % CI 1.04-1.10) higher on weekend days compared to weekdays. This was reflected in increased prescriptions for ampicillin, co-amoxiclav, nitrofurantoin, quinolones and macrolides. However, if antimicrobials were prescribed, no significant differences were observed between weekdays and weekend among the different classes of antimicrobials. GPs prescribe relatively more antimicrobials during the weekend compared to weekdays. However, the patterns of antimicrobial prescribing did not differ according to the day of prescription.