Aim: We report on an 88-year-old female patient who presented with a relapse in aqueous misdirection 15 years after being treated with pars plana vitrectomy (PPV) with hyaloidotomy-zonulectomy-iridotomy (HZI) for the same cause. Case description: A 73-year-old pseudophakic woman with a history of pseudoexfoliation underwent a trabeculectomy in the left eye in our institution because of uncontrolled intraocular pressure. Days after trabeculectomy, the patient developed aqueous misdirection and was treated with PPV combined with HZI. In the following years, the patient had regular follow-up appointments in our instruction, and she had normal intraocular pressures in the left eye without any treatment. A total of 15 years after the vitrectomy, the patient developed gradual swallowing in the anterior chamber and increased intraocular pressure. Neodymium (Nd): yttrium aluminum garnet (YAG) laser hyaloidotomy through the iridectomy opening was performed, the anterior chamber was immediately deepened, and the intraocular pressure was reduced to normal limits. The anterior chamber remained deep, and the intraocular pressure remained normal through the 36 months of follow-up. Conclusion: Relapse of aqueous misdirection may occur many years after vitrectomy, even when HZI is performed. An Nd: YAG- laser hyaloidotomy should be attempted before a second HZI is considered. Clinical relevance: A close and long-lasting follow-up of patients with aqueous misdirection is warranted, especially if the patients are treated not with complete PPV but by a limited disruption of the anterior hyaloid face along with HIZ.