This study obtained baseline information for the design of a strategy to address irrational prescribing practices in three health centers in Kampong Thom Province, Cambodia. Indicators of rational drug use have been measured and compared with Standard Guidelines. Data were collected from patients' registers and by interviewing patients immediately after patient-prescriber and patient-dispenser encounters. Checklists and pre-designed forms were used to collect data regarding the World Health Organization drug use indicators and some additional indices. Of the 330 prescriptions analyzed, the results showed that the average number of drugs per prescription was 2.35 and that a large proportion of the prescriptions contained two or more drugs that could result in adverse drug interactions. Prescribing by generic names (99.8%) was encouraging. The exposure of patients to antibiotics (66% to 100%) was high, and injection use (2.4%) was often unnecessary. Prescribing from the Essential Drugs List (99.7%) was satisfactory. The average consultation and dispensing times were short and not sufficient for patients to get health information. All the prescribed drugs were supplied, but all were inadequately labeled. Some 55% of patients knew the correct dosage of their drugs. The availability of key essential drugs (86.6%) was below the Standard. The percentages of appropriate prescriptions for treating malaria, diarrhea and acute respiratory infection treatment were 68.3%, 3.3%, and 45%, respectively. Inappropriate prescriptions were mostly due to unsuitable dosages, incorrect drugs, and the improper duration of treatment. The results suggest a need for intervention to curb the irrational use of drugs in prescribing at the three pilot health centers. Continuing education of prescribers and healthcare providers, monitoring, supervision, public education would be beneficial.