Rationale, Aims, and Objectives: Inappropriate prescribing is associated with preventable morbidity and mortality in the elderly. The American Geriatrics-Beers (AGS-Beers) Criteria was developed to guide healthcare professionals (HCPs) to prescribe medications appropriately in the elderly. However, there is a dearth of information about the knowledge and awareness of HCPs of these criteria, and their perceptions of appropriate prescribing in the elderly. This study aimed to evaluate the knowledge and perceptions of Nigerian and South African HCPs about appropriate prescribing in the elderly. Method: A 32-item questionnaire was self-administered among consecutively selected HCPs (physicians, nurses, and pharmacists) in one teaching hospital each in Nigeria and South Africa. Seven questions including six clinical vignettes from the 2015 AGS-Beers Criteria were used to assess the participants' knowledge.The participants' knowledge was classified based on the total score as poor (0-3), fair (4, 5), and good (6, 7). The HCPs' perceptions of appropriate prescribing in the elderly were evaluated using a 5-point Likert scale. Mann-Whitney U test was used to evaluate ranked variables at P < .05. Results: A total of 369 participants, 62.9% (232/369) mean age 42.75(9.35) years in Nigeria and 37.1% (137/369), mean age 38.66 (7.76) years, (CI = 2.32-5.87, P < .001) in South Africa were evaluated. Many participants in Nigeria (52.6%) and 48.2% in South Africa had scores (4, 5).The majority of the participants (57.3%) in Nigeria and 67.2% in South Africa were not aware of any explicit criteria for prescribing to the elderly while 45.8% of the total participants with no significant difference between the groups (P = .332) "strongly agreed" or "agreed" that the basic professional training is adequate for prescribing medicines to the elderly. Conclusions: Many HCPs in Nigeria and South Africa had a fair knowledge of appropriate prescribing to the elderly and considered basic professional training as adequate for appropriate prescribing to the elderly.