OBJECTIVES: To investigate doctors’ perceptions towards factors underlying irrational prescribing practices in treatment of malaria in Pakistan. METHODS: A qualitative study with snowball sampling technique was used to identify nineteen doctors working at hospitals in Islamabad and Rawalpindi. Semi-structured interviews were conducted with the doctors until the point of saturation was obtained. The interviews, which were audio-taped and transcribed verbatim, were evaluated by thematic content analysis and by other authors’ analysis. RESULTS: Thematic content analysis identified three major themes and several subthemes: 1) Factors responsible for irrational prescribing practices in treatment of malaria; 2) Lack of implementation of standard malaria treatment guidelines in the country; and 3) Strategies to improve irrational prescribing practices in treatment of malaria. All the doctors agreed on lack of implementation of standard guidelines in treatment of malaria while mixed responses were observed regarding factors influencing rational prescribing. Influence of pharmaceutical industry and unsupervised polytherapy were cited as major determinants for irrational prescribing practices in case of malaria. CONCLUSIONS: The findings suggest that the doctors in Pakistan are aware of irrational prescribing practices and its consequences in treatment of malaria but are facing significant barriers in terms of improving the current prescribing practices. There is an urgent need to design strategies such as implementation of standard malaria treatment guidelines, revision of health policies and up gradation of education and training of health players in order to improve the current prescribing practices for antimalarials.