With the advance of new exploration and production technologies, oil and gas production has gone to deeper and tighter formation than ever before. These developments have also brought challenges in scale prediction and inhibition, such as how to prevent scales at high temperature (150–200°C), pressure (1,000–1,500 bars) and TDS (>300,000 mg/L) commonly experienced at these depths. This paper will discuss (1) the challenges of scale prediction at high temperature, pressure, and TDS; (2) an efficient method to study the nucleation kinetics of scale formation and inhibition at these conditions; (3) the kinetics of barite crystal nucleation and precipitation in the presence of various scale inhibitors and the effectiveness of those inhibitors. In this study, nine scale inhibitors have been evaluated at 70–200°C to determine if they can successfully prevent barite precipitation. The results show that only a few inhibitors can effectively inhibit barite formation at 200°C. Although it is commonly believed that phosphonate scale inhibitors may not work for high temperature inhibition applications, the results from this study suggest barite scale inhibition by phosphonate inhibitors was not impaired at 200°C under strictly anoxic condition and in NaCl brine. However, phosphonate inhibitors can precipitate with Ca2+ in a brine at high temperatures and, hence, reduce efficiency. In addition, the relationship of scale inhibition to types of inhibitors and temperature are explored in this study.