OBJECTIVES: The study focus was to evaluate and compare the prescriptions for the encountered potential drug-drug interactions (pDDIs) and their different levels on the basis of onset, severity and documentation status, in a tertiary care hospital and community pharmacies in Bahawalpur, Pakistan.  METHODS: Total 800 prescriptions, 400 from a tertiary care teaching hospital and 400 from community pharmacies, fulfilling inclusion criteria were collected thrice a week during a period of three months and were analyzed for potential drug-drug interactions using dug digest database, drug interaction checker of www.drugs.com and reference text Drug Interaction Facts. RESULTS: A highly significant difference was observed between the prevalence of pDDIs in prescriptions from hospital (45%; 180 out of 400 prescriptions with at least 1 pDDI) and community pharmacies (29.25%; 117 out of 400 prescriptions with atleast 1 pDDI). On the whole, out of total 543 pDDIs (hospital = 337; community = 206) majority of them were of delayed onset (hospital = 50.44%, community = 44.66%), moderate severity (hospital = 57.87%, community = 42.72%), suspected type (hospital = 27.6%) and possible documentation (community = 14.08%). Most of the prescriptions (hospital = 80%; community = 83%) contained 2-4 medicines. The interacting combinations such as aspirin-clopidogrel omeprazole-clopidogrel and digoxin-furosemide (in hospital); isoniazid-rifampin and tramadol-escitalopram were found to be frequently involved in major interactions. The findings showed that cardiovascular drugs were involved in most of the rapid pDDIs (in hospital = 32.46%; in community = 33.33%) and respiratory system drugs were associated with majority of established documented pDDIs (in hospital = 16.67%; in community = 42.86%). CONCLUSIONS: Drug-drug interactions in prescription medicines were observed in high percentage both in hospitals and community pharmacies. Clinical practices must be standardized as rational prescribing practices.