Objective Drug-disease interactions (DDSIs) are present when a drug prescribed for one disease worsens a concomitant disease. The prevalence of DDSIs in older patients in primary care is largely unknown, as well as to what extent physicians individualize drug prescribing in relation to concomitant diseases. We therefore analysed the prevalence of DDSIs in older patients in primary care and explored to what extent physicians take possible DDSIs into account when prescribing. Design and Setting:Cross-sectional population-based register study in primary care in Region Stockholm, Sweden. Thirty-one DDSIs derived from Irish STOPP-START-Criteria were assessed. We derived data from a regional administrative healthcare database including information on all healthcare consultations and dispensed prescription drugs in the region. Data on demography, diagnoses, drug dispensations and healthcare consumption were extracted. Drugs were assessed during 2016. Subjects A total of 336,295 patients aged >= 65 registered with one of the 206 primary care practices in Region Stockholm. Main outcome measures Prevalence and prevalence differences for DDSIs. Results In 10.8% of older patients, at least one DDSI was observed. Non-steroidal anti-inflammatory drugs (NSAIDs) were implicated in more than 75% of cases. The most common DDSI was NSAID/hypertension (8.1%), followed by NSAID/cardiovascular disease and loop diuretics/urinary incontinence (both 0.7%). The use of NSAIDs among patients with heart failure or impaired renal function was 15% lower than among patients without these diseases. Conclusion DDSIs were present in every tenth older patient in primary care. Patients with cardiovascular disease receive NSAIDs to a lower extent, possibly indicating physician awareness of DDSI.