Background/Objectives: Most metacarpal fractures are isolated, simple, closed, and stable fractures and located distally. They are often caused by accidental falls, strikes by humans, by objects or traffic accidents. The majority can be treated conservatively. When unstable, angulated, malrotated or shortened, a surgical fixation of these frequent fractures is needed. To treat simple, spiral, distal or shaft fractures, intramedullary Kirschner wiring (KW) or intramedullary compression screws (ISs) are used. We wanted to compare the outcomes of those two treatments. Methods: In a retrospective study we analyzed the prospectively collected data of our hospital on the indication factors and outcome factors of selected patients with simple or spiral, distal or shaft metacarpal fractures of the second to fifth finger. Indication factors were sex, age, profession, hand dominance, comorbidities, metacarpal finger number, total active range of motion (TAM), rotation, soft tissue damage, localization, articular involvement, fracture type, dislocation and axial shortening. Outcome factors were TAM, rotation, splint time, return to work, bone healing and complications. Results: Out of 750 patients, 59 fractures could be included in this study, containing 34 in the KW Group and 25 in the IS Group. Only fracture localization and fracture type were significantly different in the two groups, with more shaft and spiral fractures in the IS Group. The primary outcome of TAM and rotation as well as the secondary outcome of splint time, return to work, bone healing and complication rates showed no significant difference. Only a difference in mean follow-up time was seen. Conclusions: Intramedullary screw fixation seems a valid alternative to KW fixation for certain fracture types regarding active range of motion and rotation after treatment, splint time, bone healing and return to work time. Only the tendency of an earlier return to work and a higher rate of full TAM after treatment was seen in favor of intramedullary screws.