Objective: To investigate the efficacy and safety of phacoemulsification combined with supra-capsular and scleral-fixated intraocular lens (IOL) implantation in the treatment of microspherophakia (MSP). Methods: by retrospective analysis, 37 MSP patients (37 eyes) who were treated in our hospital from January 2019 to June 2020 were randomly divided into two groups, including 20 MSP patients (20 eyes) who treated by SCSF-IOL and 17 MSP patients (17 eyes) who treated by transscleral-fixated modified capsular tension ring and in-the-bag intraocular lens implantation (MCTR-IOL). The best corrected vision and complications were observed. Results: the best corrected vision was significantly improved in both groups (P < 0.001), but there was no remarkable difference between the two groups (P = 0.326). The IOL tilt was also comparable (P = 0.216). Prophylactic Nd: YAG laser posterior capsulotomy was performed from 1 week to 1 month after the SCSF-IOL procedure. In the SCSF-IOL group, two eyes (10.00%) needed repeated laser treatment, and one eye (5.00%) had a decentered capsule opening. Posterior capsular opacification was the most common complication (6, 35.29%) in the MCTR group. No IOL dislocation, secondary glaucoma, or retinal detachment was observed during follow-up. Conclusions: SCSF-IOL is a simple and viable surgical option for managing MSP and is comparable with the MCTR-IOL. Nd: YAG laser posterior capsulotomy is a necessary mean to prevent residual capsule complications after the SCSF-IOL procedure.