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Heterotopic ossification (HO) is a common disturbing complication of intra‐articular fractures. Its prevention and treatment are still difficult as its pathogenesis is unclear. It was reported that PDGFRα+ muscle cells in skeletal muscle may participate in the formation of HO; however, the specific mechanism is still unknown. This study investigated the function of miR‐19b‐3p in osteogenic differentiation of PDGFRα+ muscle cells. MiR‐19b‐3p was upregulated during PDGFRα+ muscle cell osteogenic differentiation. The exogenous expression of miR‐19b‐3p led to an increase in osteogenic marker gene transcription and translation during the osteogenic differentiation of PDGFRα+ muscle cells. Furthermore, both alkaline phosphatase and alizarin red staining increased in miR‐19b‐3p mimic transfected cells. Over‐expression of miR‐19b‐3p led to the down‐regulation of gene of phosphate and tension homology deleted on chromosome ten (PTEN). Additionally, the dual luciferase reporter assay demonstrated that PTEN was a direct target of miR‐19b‐3p. The increase of osteocalcin, osteopontin, and Runt‐related transcription factor 2 protein levels induced by ectopic miR‐19b‐3p expression could be partially reversed by PTEN over‐expression. In conclusion, our results suggested that miR‐19b‐3p may be a promising target in inhibiting PDGFRα+ muscle cell osteogenic differentiation and treatment of HO. [ABSTRACT FROM AUTHOR]