Background: To evaluate whether ongoing axonal loss can be prevented in multifocal motor neuropathy (MMN) treated with immunoglobulin G (IgG), a group of patients with a median disease duration of 15.7 years (range: 8.3–37.8), treated with titrated dosages of immunoglobulins, was studied electrophysiologically at time of diagnosis and at follow-up. Results: At follow-up, the Z-score of the compound motor action potential amplitude of the median, fibular, and tibial nerves and the neurological performances were determined. In seven patients with a treatment-free period of 0.3 years (0.2–0.4), there was no progression of axonal loss (p = 0.2), whereas a trend toward further axonal loss by 1.3 Z-scores (0.9–17.0, p = 0.06) was observed in five patients with a treatment-free period of 4.0 years (0.9–9.0). The axonal loss in the group with a short treatment delay was significantly smaller than in the group with a longer treatment delay (p = 0.02). Also, there was an association between treatment delay and ongoing axonal loss (p = 0.004). The electrophysiological findings at follow-up were associated with the isokinetic strength performance, the neurological impairment score, and the disability, supporting the clinical relevance of the electrophysiological estimate of axonal loss. Conclusion: Swift initiation of an immediately titrated IgG dosage can prevent further axonal loss and disability in continuously treated MMN patients.