Alpha-calcium sulfate hemihydrate (α-HH) has been used effectively in grafting through its desired features to support bone regeneration. In recent years, many synthetic methods have been proposed. Among them, the autoclave method for manufacturing α-HH is best suited for cost-savings due to its simple operation and limited use of additives. Despite these advantages, the synthesis of surgical grade products without the use of any additives has not yet been clearly discussed. In this study, surgical grade α-HH was successfully produced from calcium sulfate dihydrate (DH) using the autoclave method at an elevated temperature and pressure. The synthesized powder had a high purity of about 98.62% α-HH with a prismatic morphology (20.96 ± 8.83 µm in length and 1.30 ± 0.71 µm in diameter). The screening tests, in simulated body fluid (SBF) solution, for the product properties showed no bioactivity, and fast degradation accompanied by a slight decrease in pH. The lactate dehydrogenase (LDH) assay showed good biocompatibility of the material, however, its potential for cytotoxicity was also observed in NIH 3T3 cells. Briefly, despite some unfavorable properties, the autoclave-synthesized α-HH is a promising bone graft substitute that can be applied in orthopedic and maxillofacial surgeries.