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Lateral malleolus fracture is one of the most common fractures. However, there is controversy regarding the rehabilitation protocols used after surgery. In particular, the initiation point for weight-bearing has not been standardized. In the present study, we investigated the prognostic difference between immediate and delayed weight-bearing on lateral malleolus fractures. The medical records of matched patients in the immediate and delayed weight-bearing groups (50 and 50, respectively) were reviewed retrospectively. All patients were treated with open reduction and internal fixation using an anatomical locking compression plate with a lag screw. In the immediate weight-bearing group (IWB), tolerable weight-bearing (i.e., what can be endured immediately after surgery with crutches) was permitted. In the delayed weight-bearing group (DWB), weight-bearing was completely restricted for 4 weeks after surgery. Ankle motion exercise was permitted in both groups, starting from the day after surgery. Radiographic assessment data and clinical outcomes were reviewed between the two groups. No significant differences in radiographic assessments and complications were found between the two groups. Significant differences in terms of a shortened length of hospital stay and time to return to work with the IWB rehabilitation protocol compared with DWB were confirmed (6.0 vs. 9.2 days, p = 0.02 and 6.1 vs. 8.3 weeks, p = 0.02, respectively). A significant difference in sport factor was observed in the Foot and Ankle Outcome Score at 3 months postoperatively (72.3 vs. 67.4, p = 0.02). We found no significant differences between the two groups concerning postoperative radiological outcomes and complications. The benefits of shortening the time to return to work and length of hospital stay associated with the IWB rehabilitation protocol were confirmed. In conclusion, immediate weight-bearing is recommended in patients with lateral malleolus fracture after anatomical reduction and firm fixation by surgery.