IntroductionOpen reduction internal fixation (ORIF) and intramedullary nail fixation (IMN) are the predominant repair methods for operative treatment of humeral diaphyseal fractures; however, the optimal method is not fully elucidated. The purpose of this study was to analyze whether IMN or ORIF humeral diaphyseal surgeries result in a significantly higher prevalence of adverse outcomes and whether these outcomes were age dependent. We hypothesize there is no difference in reoperation rates and complications between IMN and ORIF for humeral diaphyseal fractures.MethodsData collected from 2015 to 2017 from the Nationwide Readmissions Database were evaluated to compare the prevalence of six adverse outcomes: radial nerve palsy, infections, nonunion, malunion, delayed healing, and revisions. Patients treated for a primary humeral diaphyseal fracture with either IMN or ORIF were matched and compared (n= 2,804 pairs). Patients with metastatic cancer were excluded.ResultsFollowing an ORIF procedure, there was a greater odds of undergoing revision surgery (p= 0.03) or developing at least one of the complications of interest (p= 0.03). In the age-stratified analysis, no significant differences were identified in the prevalence of adverse outcomes between the IMN and ORIF cohorts in the 0–19, 20–39, and 40–59 age groups. Patients who were 60 + had 1.89 times the odds of experiencing at least one complication and 2.04 times the odds of undergoing a revision after an ORIF procedure versus an IMN procedure (p= 0.03 for both).DiscussionIMN and ORIF for humeral diaphyseal fractures are comparable in regard to complications revision rates in patients under the age of 60. Meanwhile, patients 60 + years show a statistically significant increase in the odds of undergoing revision surgery or experiencing complications following an ORIF. Since IMN appears to be more beneficial to older patients, being 60 + years old should be considered when determining fracture repair techniques for patients presenting with primary humeral diaphyseal fractures.Level of EvidenceIII.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13018-023-03663-2.