Purpose::Upper extremity injuries (UEIs) and lower extremity injuries (LEIs) constitute a considerable component of traumas. However, their epidemiologic differences and short-term in-hospital outcomes are not fully elucidated. This study aims to compare such discrepancies in a large-scale study.Methods::In this retrospective study, all patients with UEIs and/or LEIs hospitalized from 24th July 2016 to 16th May 2020 in Sina Hospital, Tehran, Iran, and registered at the National Trauma Registry of Iran were enrolled in the study. Relevant demographic and clinical characteristics were extracted from the National Trauma Registry of Iran database. Patients were grouped into either UEI or LEI. For those with concomitant UEIs and LEIs, the more severe one based on the abbreviated injury scale was defined as the principal diagnosis. In addition, cases with the abbreviated injury scale > 3 for both UEI and LEI or concomitant injuries to body areas other than the limbs were excluded. Independent samples t-test, Mann-Whitney U test, Chi-square test, quintile regression models, and logistic regression models with "margins" command were used for statistical analyses, as indicated. Results::In this research, 3170 eligible cases were identified. For the LEI group, there was a much higher proportion of male patients (86.7% vs. 82.0%) and higher mean age (years, 42.9 vs. 35.3) compared to the UEI group (both p < 0.001). Patients with an injury severity score (ISS) of 9 -15 were outnumbered in the LEI group (22.9% vs. 1.6%, p < 0.001), while the proportion of those with an ISS < 9 was higher in the UEI group (98.1% vs. 76.8%, p < 0.001). The multiple logistic regression model showed a statistically significant association between intensive care unit (ICU) admission and ISS (odds ratio ( OR)=4.01 for ISS 9 -15 vs. ISS < 9, 95% confidence interval ( CI)): 3.01 -5.35; OR =17.65 for ISS ≥ 16 vs. ISS < 9, 95% CI: 4.03 -77.27), age ( OR =1.02, 95% CI: 1.01 -1.03), cause of injury ( OR =0.27 for blunt trauma vs. road traffic crash, 95% CI: 0.08 -0.90; OR =0.49 for cut/stab injuries vs. road traffic crash, 95% CI: 0.28 -0.84) and body region ( OR=1.65 for lower extremity, 95% CI: 1.19 -2.29). Having adjusted for other covariates, the odds of ICU admission in patients with LEIs was 1.65 times the odds in patients with UEIs. Conclusions::Patients with LEIs were older and suffered from more severe injuries. In addition, the age-and ISS-adjusted ICU admission and length of hospital stay were significantly higher in LEI patients. The chance of ICU admission was associated with age, cause of injury, ISS, and body region. The findings of this study can aid in the meticulous selection of ICU-candidate patients. In addition, the role of factors other than ISS and age in ICU admission and prolongation of hospitalization should be addressed by prospective studies.