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Medication discontinuation poses a significant challenge to the effectiveness of therapeutic interventions and overall patient treatment outcomes. Improving the pharmaceutical dosage forms' acceptability for patients, knowledge of proper ways for medication usage, and proper storage of medications play an indispensable role in enhancing patient safety. Thus the present study aimed to assess patients' preferences for pharmaceutical dosage forms, their knowledge of storage of medications, and factors associated with medication discontinuation among patients attending Red Cross pharmacies in Northwest Ethiopia. This multicenter cross-sectional study was conducted from January 16, 2024, to February 15, 2024. The collected data was entered into EpiData (version 4.6.0) and statistical analysis was carried out by exporting to STATA version 14. A p-value of less than 0.05 was statistically considered as significant. Among 388 study participants, more than half (54.4%) had a history of medication discontinuation and frequency of administration was the most contributing factor (39.4%). The common reason for study participants' dosage form preferences was the ease of use (62.1%), followed by high efficacy and safety (11.9%). Rural residency [AOR = 1.61; 95%CI: 1.03, 2.52], number of medications [AOR = 4.29; 95%CI: 2.03, 9.06], preference for the type of dosage forms [AOR = 5.86; 95% CI: 3.36, 10.21], and frequency of administration [AOR = 2.49; 95%CI: 1.55, 3.99] were factors significantly associated with medication discontinuation. The present study revealed that more than half of the study participants had a history of medication discontinuation.To reduce medication discontinuation and enhance the treatment outcome of patients, medical and pharmacy professionals should improve information concerning dosage forms and their acceptability for patients through ongoing patient education and training., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical considerations: Ethical clearance for the present study was obtained from the Institutional Review Board of Debre Tabor University College of Health Sciences with reference number DTU/RES/305/24. Informed written consent was obtained from the participants. Throughout the study period, confidentiality was maintained. In addition, study participants were given education on how to take medications and the impact of medication discontinuation on their treatment outcome and we informed them that they should tell their healthcare practitioners about their preference for pharmaceutical dosage forms. All methods of this study were based on the declaration of Helsinki., (© 2024. The Author(s).)