BACKGROUND: Sub-Saharan Africa (SSA) faces the highest rate of hypertension worldwide. The high burden of elevated blood pressure (BP) in black people has been emphasized. Guidelines recommend two or more antihypertensive medications to achieve a BP control. We aimed to identify factors associated with prescription of up-titrated antihypertensive strategies in Africa. METHODS: We conducted a cross-sectional study on outpatient consultations for hypertension across 12 SSA countries. Collected data included socioeconomic status, antihypertensive drugs classes, BP measures, cardiovascular risk factors and complication of hypertension. We used ordinal logistic regression to assess factors associated with prescription of up-titrated strategies. RESULTS: The study involved 2123 treated patients with hypertension. Patients received monotherapy in 36.3 vs. 25.9%, two-drug in 42.2 vs. 45% and three and more drugs strategies in 21.5 vs. 29.1% in low (LIC) and middle (MIC) income countries, respectively. Patients with sedentary lifestyle [OR 1.4 (1.11-1.77)], complication of hypertension [OR 2.4 (1.89-3.03)], former hypertension [OR 3.12 (2.3-4.26)], good adherence [OR 1.98 (1.47-2.66)], from MIC [OR 1.38 (1.10-1.74)] and living in urban areas [OR 1.52 (1.16-1.99)] were more likely to be treated with up-titrated strategies. Stratified analysis shows that in LIC, up-titrated strategies were less frequent in rural than in urban patients (P for trend <0.01) whereas such difference was not observed in MIC. CONCLUSION: In this African setting, in addition to expected factors, up-titrated drug strategies were associated with country-level income, patient location and finally, the interplay between both in LIC. These results highlight the importance of developing policies that seek to make multiple drug classes accessible particularly in rural and LIC.