Introduction: The small size of Short Tandem Repeats (STRs), their ubiquitous genome-wide distribution and polymorphic nature enhances their value in human forensic/population genetics applications. Objectives: This study aims to investigate the short tandem repeat variation based on 15 loci in a population from the central region of Saudi Arabia. Methods: Allele frequency variation for 15 Short Tandem Repeat (STR) loci was examined in 190 unrelated Saudi volunteers. Results: This study summarizes the allele distribution in the Saudi population and compares them to other populations located in Asia, Africa, the Middle East and Europe. The standard forensic parameters of Observed Hetrozygosity (Ho), Expected Heterozygosity (He) and Gene Diversity Index (GD) were determined for the following 15 STR loci: D8S1179, D21S1, D7S820, CSF1PO, D3S1358, TH0, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S5, D5S818 and FGA. The most frequent alleles in the Saudi population were: 8 repeats (0.558) at TPOX, 12 (0.411) at D13S317, 12 (0.385) at CSF1PO, 11 (0.382) at D16D539 and 10 (0.358) at D7S820. The 15 markers utilized in this study are highly informative as evidenced by their high power of discrimination (PD) values with D2S1338, D19S433 and FGA having the highest PD values. The relationship between the Saudi population and other geographically distributed populations, assessed by a Multidimensional Scaling (MDS) plot, showed that the Saudi population clustered with groups from Yemen, Iraq, Qatar, Oman and Bahrain. Conclusion: TPOX, D13S317, CSF1PO, D16D539 and D7S820 markers were found suitable for forensic analysis, paternity testing and can also be used for chimerism study after allogenic bone marrow transplantation for Saudi population. On the other hand, the population admixture with other ethnic origins might explain the variable degree of genetic distances of this population and other Arab-related groups.