Purpose: To evaluate the postoperative effects of topical coenzyme Q10 + vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (CoQ10) after cataract surgery. Methods: 40 consecutive patients were randomized to receive CoQ10 or saline solution (SS) twice daily for 9 months after uneventful cataract surgery with a temporal port. Before surgery, on day 14 and at months 3, 6 and 9, they underwent non-invasive break-up time (NIBUT) testing, Schirmer test, BUT, aesthesiometry as well as in vivo confocal microscopy of the subbasal nerve plexus of the cornea (SBP). The density of the subbasal nerves was calculated in the central (CFD) and temporal (TFD) cornea (number of fibres per field). Results: On day 14, surgery reduced CFD and TFD, respectively, by 25–35 and 50%; indices of ocular surface stability were all impaired. The treatment with CoQ10 was associated with faster nerve regeneration than SS (at month 3, CFD +1.5 ± 1.9 vs. +0.2 ± 1.8, p = 0.04, and TFD +2.5 ± 1.7 vs. +1.0 ± 1.6, p = 0.007; at month 6, TFD +2.7 ± 1.9 vs. +1.4 ± 1.5, p = 0.02) and better stability of ocular surface (NIBUT and BUT) throughout the study. No relevant side effects were found, apart from occasional burning in 10% of CoQ10 patients. Conclusions: Changes of the corneal nerves occurring after cataract surgery may influence the integrity of the ocular surface. Treatment with topical CoQ10 has a positive effect in restoring SBP anatomy and ocular surface stability.