Growth hormone deficiency (GHD) is an endocrine disorder characterized by insufficient production of growth hormone (GH). PEGylated recombinant human growth hormone (PEG-rhGH; Jintrolong (R), GeneScience Pharmaceuticals Co., Ltd.) is the only long-acting GH approved in China for treating paediatric GHD (PGHD). Long-term Efficacy and Safety Evaluation of Growth Hormone in Children in China (CGLS) is a large, surveillance registry database of participants with short stature treated with PEG-rhGH or rhGH in a real-world setting. In this study, we evaluated the safety profile and five-year growth response of PEG-rhGH based on the data from the CGLS database in participants with PGHD in China. In this real-world registry-based observational study, a total of 1,207 participants were included in the safety analysis set. Of these, 339 participants who had received PEG-rhGH continuously for five years were also included in the efficacy analysis. Key outcomes assessed comprised adverse events (AEs), serious AEs (SAEs), and height gain. The safety assessment indicated that 563 participants exhibited 1328 AEs with an incidence rate of 46.6%. Furthermore, SAEs occurred in 1.0% of participants (n = 12), with none of them associated with PEG-rhGH treatment. A significant increase in mean change in height-SD score (triangle Ht SDS) was observed during the treatment period, with a mean triangle Ht SDS of 2.1 +/- 0.9 in five years. Subgroup analysis showed that the younger participants exhibited a more favourable response to therapy.Conclusion: CGLS data showed that five-year PEG-rhGH treatment in children with PGHD was associated with a favourable safety profile and sustained height gain.What is Known:center dot Several long-acting growth hormones (LAGH) have been approved for use in PGHD. PEGylated recombinant growth hormone (PEG-rhGH) is the only LAGH marketed in China, with its three-year efficacy and safety have been reported.What is New:center dot Data from the CGLS database confirms that PEG-rhGh has an acceptable safety profile over five years, with significant improvement in height. Importantly, the data indicate that initiating the treatment earlier yields better outcomes.