Introduction: Irrational prescription of drugs is still a public health issue, especially in low- and middle-income countries. This study aimed to assess prescribing quality using WHO indicators and identify factors associated with antibiotic prescribing at first-line health facilities in the city of Kisangani, the Democratic Republic of Congo. Methods: We conducted a cross-sectional study from 1 July 2019 to 30 June 2020. Using systematic sampling, we selected 21 first-line health facilities and 715 outpatient consultation forms. We then performed univariate, bivariate, and multivariate analyses using Epi Info7 and OpenEpi 3.01. Results: The average number of drugs prescribed per consultation was 4.0 (SD=1.5); the percentages of consultations with an antibiotic and an injection prescribed were 69.2% and 69.5%, respectively; 75.2% of drugs were prescribed by generic name, and 83.5% were from the national essential drugs list. Factors associated with antibiotic prescribing were the absence of care flowcharts in health facilities (OR= 0.36, 95%CI= 0.20-0.63), two or more diagnoses (OR= 1.51, 95%CI=1.05-2.17), three or more drugs prescribed (OR=4.12, 95%CI=2.49-6.79), and more than ten years of prescriber’s professional experience (OR=1.92, 95%CI=1.33-2.78). Conclusion: The prescribing indicators did not align with WHO standards, demonstrating the poor rationality of drug prescribing behaviour. Promoting rational drug prescribing in first-line health facilities, with a particular focus on antibiotics, is necessary.