Background: Humeral shaft fractures (HSFs) represent 3% of the fractures of the locomotor apparatus, and the middle third of the shaft is the section most affected. In the majority of cases, it is treated using nonsurgical methods, but surgical indications in HSF cases are increasingly being adopted. They are most common in males between 21 and 30 years old and females between 60 and 80 years old. Objective: To compare the intramedullary nailing and plate fixation in adult humeral shaft fractures. Materials and Methods: This was a prospective comparative study carried out in the Department of Orthopedics, Jahurul Islam Medical College & Hospital, Bhagolpur, Bajitpur, Kishoregonj for 2 years based on the patient presentation at both emergency room and outpatient clinic department between June 2021 and March 2023 in which fifty adult patients with humeral shaft non-union were recruited. Coagulopathies, on drugs like steroids, anti-neoplastic that may interfere with healing and those with significant co-morbidities such as Diabetes Mellitus, Neoplasia were all excluded from the study. Results: The nailing group operated for 84.11±8.98 minutes, while the plating group took 115.66 ± 9.56 minutes. The result was statistically significant (P < 0.05). The nailing group lost 75.02 ± 9.57 mL of blood during surgery, significantly less than the plating group's 132.79 ± 8.64 mL (P < 0.05). Of the 25 patients in the plating group, nine (36%) had outstanding results and eight (32%) had good results. In the nailing group, 11 (44%) achieved great outcomes, and 9 (36%) had good results. The two groups did not differ statistically from one another. Conclusion: The nailing group required less operating time and had less blood loss than the plating group. There were no significant differences in functional outcomes between the intramedullary nailing and plating groups.