OBJECTIVES/HYPOTHESIS To assess safety and efficacy of a steroid-releasing implant in improving surgical outcomes when placed in the frontal sinus opening (FSO) following endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). STUDY DESIGN Prospective, multicenter, randomized, blinded trial using an intrapatient control design. METHODS Eighty adult (≥ 18 years) CRS patients who underwent successful bilateral frontal sinusotomy were randomized to receive a steroid-releasing implant in one FSO, whereas the contralateral control side received no implant. All patients received standard postoperative care. Endoscopic evaluations recorded at 30-days postendoscopic sinus surgery (ESS) were graded real time by clinical investigators and by an independent, blinded sinus surgeon to assess the need for postoperative interventions in the FSO. RESULTS Implants were successfully placed in all 80 frontal sinuses, resulting in 100% implant delivery success. At 30-days post-ESS, steroid-releasing implants provided a statistically significant (P = 0.0070) reduction in the need for postoperative interventions compared to surgery alone by an independent reviewer, representing 38% relative reduction. Clinical investigators reported statistically significant reduction in this measure at 30 days (P < 0.0001) and 90 days (P = 0.0129). Clinical investigators also reported a 55.6% reduction in the need for oral steroid interventions (P = 0.0015), 75% reduction in the need for surgical interventions (P = 0.0225), 16.7% reduction in inflammation score, 54.3% reduction in restenosis rate (P = 0.0002), and 32.2% greater diameter of FSO (P < 0.0001) on treated sides compared to control at 30 days. No implant-related adverse events were reported. CONCLUSION This study demonstrates the efficacy of steroid-releasing implants in improving outcomes of frontal sinus surgery. LEVEL OF EVIDENCE 1b. Laryngoscope, 126:2659-2664, 2016.