Rational use of therapeutic agents is a vital component of good health outcomes for patients as well as the community. The current study aimed to identify rational use of drugs, prescription errors and polypharmacy in outpatients at a teaching hospital in Khyber Pakhtunkhwa, Pakistan. A prospective cohort research study was conducted for analyzing prescription in the outpatient pharmacy department of Lady Reading Hospital, Khyber Pakhtunkhwa, Pakistan. A total of 326 prescriptions were examined through a random systematic sampling method. World Health Organization (WHO) core drug prescribing indicators and prescription legibility methods were used for prescription analysis. Using SPSS version 22.0, the collected data were recorded and analyzed after manual data verification. Of the total, 1,539 drugs were prescribed with a mean drug per prescription of 4.7 (Optimal value ≤ 2). Out of these, 65.3% (Optimal value < 30%) prescriptions consisting of antibiotics, Prescriptions with injectab