Purpose: To compare the safety and efficacy of an intraoperative transzonular injection of triamcinolone-moxifloxacin (Imprimis' Tri-Moxi 15 mg/1 mg/mL) to topical drops in patients undergoing cataract surgery. Methods: Between January 2017 and October 2017, patients undergoing phacoemulsification cataract surgery by a single surgeon at the Penn State Eye Center were offered a single intraoperative injection of transzonular triamcinolone-moxifloxacin in lieu of perioperative drops. Between November 2017 and July 2018, the transzonular injection was not offered, and all patients who underwent surgery by the same surgeon received a drop regimen consisting of polymyxin b/trimethoprim and prednisolone acetate 1%. Patients were seen 1 day, 1 week, and 6-9 weeks postoperatively. Outcome measures included incidence of intraoperative complications, postoperative breakthrough inflammation, cystoid macular edema, and infectious sequela. Results: Of the 198 eyes, 99 from 73 patients received the injection and 99 from 82 patients received topical drops. One (1%) intraoperative posterior capsule tear occurred in each group. Eleven (11.1%) eyes in the injection group and 3 (3%) in the drop group experienced symptomatic breakthrough inflammation necessitating treatment (P = 0.0488). One (1%) eye in the injection group and zero (0%) in the drop group developed clinically significant macular edema (P = 1.0). No instances of elevated intraocular pressure or infectious sequela occurred in either group (P = 1.0). Conclusions: Transzonular injection of triamcinolone-moxifloxacin may be associated with an increased incidence of breakthrough inflammation compared to topical drops.