Rationale and Objective: IgA nephropathy (IgAN) is an important cause for end-stage renal disease worldwide. The treatment for IgAN remains challenging, and few randomized and controlled clinical trials have been conducted to evaluate new therapies. The present study assesses the efficacy and safety of Abelmoschus manihot (AM) in IgAN patients. Study Design: Randomized, non-inferiority, double-blind, double-dummy multicenter trial. Setting and Participants: This trial was designed to recruit 1,600 biopsy-proven IgAN patients (proteinuria between 0.5-3.0 g/d and estimated glomerular filtration rate [eGFR] of >= 45 ml/min/1.73 m(2)) across China. Interventions: The participants were randomized at 1:1 to AM (2.5 g for three times per day) or losartan potassium (100 mg per day) for 48 weeks. Outcomes: The primary outcome was the change in 24-hour proteinuria from baseline to week 48. The secondary outcomes were the change in eGFR from baseline to week 48, and the incidents of endpoint events (proteinuria >= 3.5 g/24 h, doubling of serum creatinine, or receiving renal replacement treatment). Results: Among 1,470 randomized patients (mean age, 37.4 [SD, 10.6] years old; 777 [52.9%] were female; mean eGFR, 95.0 [SD, 24.3] mL/min/1.73 m(2); mean 24-hour proteinuria, 1.2 [SD, 0.7] g/d), the mean decline in 24-h proteinuria at week 48 was 230 mg and 253 mg in the AM and losartan potassium groups, respectively (P = 0.676). The mean difference in the change in 24-h proteinuria between these two groups was -23.32 mg (95% confident interval: -123.2 to 76.6, p = 0.647). The mean decline in eGFR was 0.41 ml/min/1.73 m(2) and 0.76 ml/min/1.73 m(2) in the AM and losartan potassium groups, respectively (p = 0.661). The mean difference in the change in eGFR between these two groups was -0.43 ml/min/1.73 m(2) (95% confident interval: -1.99 to 1.13, p = 0.589). The incidence of endpoint events was 8.6% in the AM group and 8.2% in the losartan group (p = 0.851). Limitations: The results of the trial may not be generalized to IgAN patients with a proteinuria of > 3.0 g/d and an eGFR of < 45 ml/min/1.73 m(2). The long-term benefits of AM in reducing the risk of progressive renal dysfunction remains unclear, based on this 48-week observation. Conclusion: AM can be recommended as a promising treatment for IgAN patients.