To compare the clinical performance of a hydrophobic (AcrySof PanOptix) and a hydrophilic (AT LISA tri 839MP) diffractive trifocal intraocular lens (IOL). Kaskaloglu Eye Hospital, Izmir, Turkey. Prospective case series. Patients had bilateral cataract surgery or refractive lens exchange with implantation of the hydrophobic diffractive IOL or hydrophilic diffractive IOL. The binocular corrected distance visual acuity (CDVA) at 4m, corrected intermediate visual acuity (CIVA) at 80cm and 60cm, and corrected near visual acuity at 40cm; low-contrast CDVA; spherical equivalent refraction; binocular corrected defocus curve; photic phenomena; and spectacle use were compared. The study comprised 238 eyes (119 patients). The mean CIVA at 60cm was better in the hydrophobic diffractive IOL group than in the hydrophilic diffractive IOL group (0.07 logarithm of the minimum angle of resolution [logMAR]±0.07 [SD] versus 0.22±0.10 logMAR; P<.001). The mean CIVA at 80cm was better in the hydrophilic IOL group (0.07±0.08 logMAR versus 0.17±0.09 logMAR; P<.001). Visual acuity at 1.00 diopter (D) to -2.50 D was significantly better in the hydrophobic diffractive group (P=.011 to <.001). The rate of severe and bothersome halos was higher in the hydrophilic diffractive group (P=.032 and P=.004, respectively). The percentage of patients reporting never using spectacles for intermediate vision was significantly higher in the hydrophobic group (P=.016). Both IOLs gave similar and favorable visual and refractive outcomes. The hydrophobic diffractive IOL might be more suitable for patients who require good closer intermediate viewing.