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Background This study examines the 20-year trend of suicide in 46 Muslim-majority countries throughout the world and compares their suicide rates and trends with the global average. Ecological-level associations between the proportion of the Muslim population, the age-standardized suicide rates, male-to-female suicide rate ratio, and the Human Development Index (HDI) in 2019 were examined. Methods Age-standardized suicide rates were extracted from the WHO Global Health Estimates database for the period between 2000 and 2019. The rates in each country were compared with the age-standardized global average during the past 20 years. The countries were further grouped according to their regions/sub-regions to calculate the regional and sub-regional weighted age-standardized suicide rates involving Muslim-majority countries. Correlation analyses were conducted between the proportion of Muslims, age-standardized suicide rate, male: female suicide rate ratio, and the HDI in all countries. Joinpoint regression was used to analyze the age-standardized suicide rates in 2000-2019. Results The 46 countries retained for analysis included an estimated 1.39 billion Muslims from a total worldwide Muslim population of 1.57 billion. Of these countries, eleven (23.9%) had an age-standardized suicide rate above the global average in 2019. In terms of regional/sub-regional suicide rates, Muslim-majority countries in the Sub-Saharan region recorded the highest weighted average age-standardized suicide rate of 10.02/100,000 population, and Southeastern Asia recorded the lowest rate (2.58/100,000 population). There were significant correlations between the Muslim population proportion and male-to-female rate ratios (r=-0.324, p=0.028), HDI index and age-standardized suicide rates (r=-0.506, p<0.001), and HDI index and male-to-female rate ratios (r=0.503, p<0.001) in 2019. Joinpoint analysis revealed that seven Muslim-majority countries (15.2%) recorded an increase in the average annual per