Importance Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, particularly in low- and middle-income countries. With advancements in neonatal care, a projected rising trend and burden of ROP-related vision loss necessitates attention. Objective To analyze global trends in ROP-related visual impairment from 1990 to 2021 and identify risk factors for increased prevalence of visual loss. Design, Setting, and Participants This cross-sectional study used the Global Burden of Disease 2021 dataset to identify ROP-related visual outcomes across 204 countries from 1990 to 2021. Socioeconomic and health care indicators were incorporated to identify risk factors for increased prevalence of visual loss, and machine-learning models were used for outcome forecasting until 2050. This analysis was conducted between January 1 and March 30, 2025. Exposure Premature birth. Main Outcome and Measures The main outcome was global prevalence of ROP-related visual impairment, stratified by severity of visual impairment and the associated factors. Results A total of 8.79 million cases of ROP-related visual loss were documented between 1990 and 2021 (4.57 million male and 4.22 million female patients), and the number of cases globally remained stable during this time. Countries with a low social demographic index (SDI) (536 899 cases; 95% uncertainty interval [UI], 418 860-655 140 cases) and low-middle SDI (802 078 cases; 95% UI, 590 539-1 032 465 cases) accounted for the majority of ROP-related visual loss cases in 2021. Despite a sharp decline since the 2000s, prevalence of ROP-related blindness remains disproportionately high in low and low-middle SDI countries. The prevalence pattern shows a shifting burden of ROP-related visual impairment, with high-middle SDI countries in particular experiencing an increasing prevalence rate in all-grade visual loss related to ROP. Multivariable regression analysis found that a lower primary completion rate (estimate, −2.33 [95% CI, −3.11 to 1.55] cases per 100 000 people), higher out-of-pocket health care expense (estimate, 2.61 [95% CI, 1.86 to 3.35] cases per 100 000 people), lower social insurance coverage (estimate, −2.79 [95% CI, −3.76 to 1.82] cases per 100 000 people), lower prenatal screening coverage (estimate, −3.91 [95% CI, −4.63 to 3.19] cases per 100 000 people) and nursing staff density (estimate, −2.07 [95% CI, −3.03 to 1.11] cases per 100 000 people) were associated with higher visual loss prevalence. Projections indicate that without targeted interventions, the burden of ROP-related visual impairment will continue to escalate, particularly in high-middle and middle SDI regions. Conclusions and Relevance This cross-sectional study found that persistent disparities in ROP-related visual loss burden remain between socioeconomic contexts and SDI groups, especially in terms of ROP-related blindness. Addressing socioeconomic disparities, enhancing neonatal care access, and implementing universal ROP screening and follow up programs might reduce the magnitude of the burden of future ROP-related visual loss.