- Abstract Purpose: Medical clowning has proven effective for reducing pain, anxiety, and stress. However, its differential effects on children from different cultures have not yet been researched. This study evaluated the effects of medical-clowning intervention on anxiety and pain among Jewish and Bedouin children and anxiety among their parents in southern Israel. Patients and methods: The study was conducted in hospital pediatric departments and employed a pre–post design involving quantitative and qualitative methods. The study included 89 children whose ages ranged from 7.5 to 12 years (39 Jewish and 50 Bedouin) and 69 parents (19 Jewish and 50 Bedouin). Questionnaires assessing pain, anxiety, and demographics were used at the pre-intervention stage and pain, anxiety, and enjoyment of different aspects of the intervention were evaluated following the intervention. The intervention stage lasted for 8–10 minutes and included the use of word play, body language and making faces, as well as the use of props brought by the clown. Semi-structured interviews were also conducted at the post-intervention stage. Results: The intervention reduced pain and anxiety among both groups of children and reduced anxiety among both groups of parents. However, anxiety levels were reduced more significantly among Bedouin children. The nonverbal components of the clowns' humor were most central, but it was the verbal components that mediated the reduction in anxiety among the Bedouin children. Conclusion: This study underscored the effectiveness and importance of medical clowning in reducing pain and anxiety among children in different cultural contexts. Moreover, the issue of culturally appropriate humor was underscored and implications for intercultural clown training are discussed.