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Background:  A 15‐fold increased risk of gastrointestinal bleeding has been reported with concurrent use of selective serotonin reuptake inhibitors and non‐steroidal anti‐inflammatory drugs. Recent guidance cautions against concurrent prescription, particularly in older people.

Aim:  To quantify the risk of gastrointestinal bleeding associated with current exposure to non‐steroidal anti‐inflammatory drugs, selective serotonin reuptake inhibitors, and both drugs concurrently.

Methods:  We conducted a case–control analysis of 11 261 cases with upper gastrointestinal bleeding and 53 156 controls matched by gender, age and general practice from computerized primary care data. We coupled this with self‐controlled case series analysis.

Results:  Both drugs were associated with a twofold increased risk of gastrointestinal bleeding (odds ratio =2.38, 95% confidence interval 2.08–2.72 for selective serotonin …