Summary Background An increase of therapeutic substitution after patent expiry might have a negative effect on cost‐savings generated with newly introduced generic drugs. To evaluate influences of patent expiry on therapeutic substitution, switch behaviour before and after patent expiry was investigated. Aim To describe proton pump inhibitor use and investigate substitution patterns from omeprazole before and after patent expiry. Methods Data were obtained from the InterAction DataBase. Proportional proton‐pump inhibitor use was identified per quarter during the study period 2000–2003. For the second part two cohorts – one before and one after patent expiry – were defined. The number of switchers was quarterly identified during 2‐year follow‐up period. For statistical analyses the chi‐square test and hazard ratio were used. Results In proportional use, a downward trend for omeprazole was found. After patent expiry, significantly more patients switched to other proton pump inhibitors ( P < 0.001). The hazard ratio of 0.62 (95% CI: 0.57–0.69), indicates that for every six patients switching before patent expiry, 10 patients switch after patent expiry. Conclusion After patent expiry more patients switch to another proton pump inhibitor. In light of the total savings achieved with generic omeprazole, the importance of this negative impact on total cost‐savings on proton pump inhibitors is unclear.