To evaluate the safety and feasibility of a new femtosecond laser-assisted method for posterior capsule opacification (PCO) prevention. University Eye Hospital Bochum, Bochum, Germany. Prospective randomized intraindividual case series. Eyes scheduled for bilateral cataract surgery between April 2015 and January 2016 were enrolled in the study. In 1 eye, routine manual cataract surgery with intraocular lens (IOL) implantation was performed with a primary posterior laser capsulotomy as the last step in the procedure. For the laser treatment, the posterior capsule between the anterior hyaloid surface and the posterior optic surface of the IOL was identified with integrated 3-dimensional spectral-domain optical coherence tomography. In the fellow eye, routine manual cataract surgery without posterior capsulotomy was performed. Follow-up examinations were done 1 week, 2 months, and 6 months after surgery. The main outcome measures were feasibility of the procedure and between-group difference in visual acuity, macular thickness, laser flare, intraocular pressure (IOP), and PCO. Fifty-six eyes were included. No differences in cataract density (P = .2), axial length (P = .8), or amount of ultrasound energy used (P = .55) were found between the groups. In all cases, it was possible to identify and target the posterior capsule. In 1 case, a minimal attachment of a half-hour length was seen. No significant between-group differences in visual acuity, macular thickness, laser flare, or IOP were seen. The described off-label use of primary posterior laser capsulotomy was a safe, feasible technique in preventing PCO over a 6-month follow-up.