Aims Stemless humeral implants have been developed to overcome stem-related complications in total shoulder arthroplasty (TSA). However, stemless implant designs may hypothetically result in less stable initial fixation, potentially affecting long-term survival. The aim of this study is to investigate early fixation and migration patterns of the stemless humeral component of the Simpliciti Shoulder System and to evaluate clinical outcomes. Methods In this prospective cohort study, radiostereometric analysis (RSA) radiographs were obtained in 24 patients at one day, six weeks, six months, one year, and two years postoperatively. Migration was calculated using model-based RSA. Clinical outcomes were evaluated using the visual analogue scale (VAS), the Oxford Shoulder Score (OSS), the Constant-Murley Score (CMS), and the Disabilities of the Arm, Shoulder and Hand (DASH) score. Results At two years, median translation along the x-, y-, and z-axis was -0.12 mm (interquartile range (IQR) -0.18 to 0.02), -0.17 mm (IQR -0.27 to -0.09), and 0.09 mm (IQR 0.02 to 0.31). Median rotation around the x-, y-, and z-axis was 0.12° (IQR -0.50 to 0.57), -0.98° (IQR -1.83 to 1.23), and 0.09° (IQR -0.76 to 0.30). Overall, 20 prostheses stabilized within 12 months postoperatively. Four prostheses showed continuous migration between 12 and 24 months. At two-year follow-up, with the exception of one revised prosthesis, all clinical scores improved significantly (median VAS difference at rest: -3.0 (IQR -1.5 to -6.0); OSS 22.0 (IQR 15.0 to 25.0); CMS 29.5 (IQR 15.0 to 35.75); and DASH -30.0 (IQR -20.6 to -41.67) (all p < 0.001)) with the exception of one revised prosthesis. Conclusion In conclusion, we found that 20 out of 24 implants stabilized within 12 months postoperatively. The significance of continuous migration in four implants is unclear and future research on the predictive value of early migration for future loosening in TSA is required. Clinical results revealed a clinically relevant improvement. Cite this article: Bone Joint J 2022;104-B(1):76–82.