Abstract Background: Osteoporosis and neurological complications are consequences of acute lymphoblastic leukemia (ALL). Collagen type I alpha 1 gene (COL1A1) polymorphism is associated with osteoporosis. This study aimed to detect the COL1A1 polymorphism and the neurological complications in ALL patients and their association with decreased lumbar spine bone mineral density (BMDLS). This study included 100 pediatric ALL patients and 100 controls. All participants were subjected to laboratory assessment and assessment of BMDLS at the start of the study and 3 years later. COLIA1 genotyping was done once for all participants. Results: At the start of the study, there was a significant decrease in osteocalcin (OC), alkaline phosphatase (ALP), and BMDLS levels in the patients. G/T variants and “T” alleles were significantly more detected in the patients (34% and 35% respectively); also, significant differences were detected between patients with polymorphism (G/T and T/ T) and those without polymorphism (G/G) regarding OC, ALP, and BMDLS. After 3 years, significant decrement in BMDLS, OC, and ALP was detected in the patients. Twenty-four patients had neurological complications and seven patients had bone fractures. Those patients had significant decrement in BMDLS, OC, and ALP levels. As regards COL1A1 gene polymorphism, the GT and TT variants were significantly detected in fractured patients, while there was no significant difference regarding GT and TT variants in the patients with neurological complications. T allele, neurological complications, high-risk stratification, and age were significantly associated with decreased BMDLS. T allele was the most significant risk factor. Conclusion: COLIA1 gene polymorphism, decreased BMDLS, and neurological complications were significantly detected in pediatric ALL patients. COLIA1 gene polymorphism is a significant risk factor for decreased BMDLS in pediatric ALL patients. There is no significant relation between COLIA1 gene polymorphism and the development of neurologic complications. Keywords: Leukemia, Osteopenia, Genetics, Polymorphism, Neurological manifestations