Objective: To investigate the relationship between transfusion frequency, serum ferritin levels, and hepatomegaly in beta-thalassemia major patients. Study Design: Cross-sectional study. Setting: Thalassemia Center, Liaquat University Hospital, Hyderabad. Period: January 2023 to June 2023. Material & Methods: Among 158 patients, age until 19 years, and β-thalassemia type major was considered as inclusion criteria. Data regarding hematological parameters and hepatomegaly was collected after informed consent. Data was analyzed using SPSS (version 22). Chi-square test was used to investigate the association between ferritin levels and hepatomegaly while Pearson’s correlation was used assess the correlation between ferritin levels and transfusion frequency. P-Value ≤ 0.05 was considered as statistically significant. Results: Majority of the participants were males (58.22%) as compared to females (41.77%). The mean age of the study participants was 9.31±4.47 years, and the mean age at first transfusion was 8.98±0.93 years. Majority of the participants were underweight 107(67.72%). Monthly transfusion rate was 1.95±0.31.The mean serum ferritin levels among the study participants were 2033.06±1309.36 ng/mL. Hepatomegaly was found to be present in 99 (62.65%) of the study participants. Statistically significant positive correlation between the frequency of transfusion and serum ferritin levels (r = 0.71, p<0.05) was observed. The difference of hepatomegaly in low-ferritin vs high-ferritin was also found to be statistically significant (p<0.05). Conclusion: It was concluded that higher transfusion rates were associated with elevated ferritin levels, and there was a significant association between higher serum ferritin levels and the presence of hepatomegaly.