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Background: Sickness absence due to non work-related conditions is a major public health issue with important socio-economic implications, and is not homogenously distributed in Spain. The objective of this study is to compare cost differences of temporary sickness absence between Barcelona and Madrid., Methods: A study was carried out based on incident cases of temporary sickness absence of more than fifteen days of duration, followed to case closure, in a retrospective cohort of workers in 2006. The study population consisted of workers of companies covered by the general regime of the Social Security System, and managed by an insurance company based in the provinces of Barcelona and Madrid in the year 2006. We compared the incidence, median duration and daily income base between Barcelona and Madrid, adjusting by sex, age and economic sector, using statistical models that take into account recurrent events in the period., Results: 24.527 cases of temporary sickness absence were identified, 62% of which originated in Barcelona. The mean cost was 33% higher in Barcelona with respect to Madrid (2.589 euros vs 1941 euros). The incidence was 22% higher in Barcelona than Madrid (1,22, IC95%: 1,10-1,36) and mean daily income base per episode was 7,80 euros higher (IC95% :7,20-8,40). In the duration the time ratio was: 1,03 ( IC95%: 1,01-1,05)., Conclusions: The higher incidence and daily income base of temporary sickness absence in Barcelona with respect to Madrid may explain the higher costs observed in the former.