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Purpose: To explore medical practitioners' perceptions towards irrational malaria treatment practices in Pakistan. Methods: A qualitative study was designed to explore the perceptions of medical practitioners regarding antimalarial prescribing practices in two major cities of Pakistan, namely, Islamabad (national capital) and its twin city, Rawalpindi. Semi-structured interviews were conducted using in-depth interview guides to collect data. Nineteen interviews with doctors working at different public and private hospitals in Islamabad and Rawalpindi were conducted at a place and time convenient for the respondents. The interviews were audio-taped, transcribed verbatim, and evaluated by thematic content analysis and other author analysis. Results: The interviews focused on three major components, i.e., treatment practices in malaria and influencing factors, role of Malaria Control Program, and suggestions for improvements. Thematic content analysis of these components yielded further themes: (1) Prevalence of malaria, (2) Common trends of treatment, (3) Current scenario of rational drug use, (4) Major contributing factors to irrational drug use, (5) Use of antibiotics, (6) Role of healthcare system, (7) Role of Malaria Control Program, (8) Role of hospital pharmacist, (9) Collaborative efforts of doctors and pharmacists in promoting rational treatment practices, and (10) Strategies to improve current treatment practices. Conclusion: The current study showed that all the respondents in the two cities agreed that irrational prescribing practices, unavailability of drugs, lack of awareness and adherence of prescribers to standard treatment guidelines, are the major factors contributing to irrational drug use in malaria in Pakistan. [ABSTRACT FROM AUTHOR]