BackgroundPatient understanding of health information is crucial for successful pharmaceutical care. Pharmaceutical pictograms enable communication of medication instructions to patients who may not share a common language or are illiterate. However, cultural factors can impact the accurate interpretation of these visual aids. ObjectivesThis study aimed to assess and compare the comprehensibility of two sets of pictograms from different cultural backgrounds among sub-Saharan migrants recently arrived in Europe. MethodsIn June 2022, a cross-sectional survey was conducted at the Migrant Temporary Stay Center in Melilla, Spain. Participants were randomly assigned to interpret 10 pictograms from either the U.S. Pharmacopeia or South African counterparts, with a minimum of 50 participants per group. Following the International Organization for Standardization's testing comprehensibility criterion, pictograms achieving a 66.7% correct interpretation rate were considered acceptable. Health literacy was measured using a culturally validated sub-Saharan version of the European Health Literacy Survey Questionnaire (HLS-EU-Q16). Data analysis included Fisher's exact test or chi-square test (for qualitative variables) and the Mann-Whitney test (for quantitative variables). ResultsA total of 106 participants were included (51 in the U.S. pharmacopeia group and 55 in the South African group). None of the assessed pictograms met the comprehensibility criterion, and both groups exhibited high nonresponse rates. The South African pictograms were better understood than the American ones for all intended messages, with a statistically significant difference in overall comprehension (p = 0.002). Additionally, the participants' country of birth was a statistically significant factor for comprehension (p = 0.019). ConclusionsOur findings indicate that evaluated pharmaceutical pictograms cannot be validly used in newly arrived sub-Saharan immigrants in Europe. However, the significantly better comprehension of South African pictograms compared to North American ones highlights the importance of cultural alignment between pictograms and their prospective users for effective comprehensibility.