There is no report on the effects of sustained low-efficiency dialysis (SLED) plus hemoperfusion (HP) (SLED + HP) in patients with acute severe organophosphate (OP) poisoning (ASOPP). This study was designed to compare the therapeutic effectiveness between SLED + HP and continuous hemofiltration (CHF) plus HP (CHF + HP) in patients with ASOPP. In order to assess the two treatment methods, 56 patients with ASOPP were divided into CHF + HP group and SLED + HP group. The biochemical indicators, in-hospital duration, hemodynamic parameters, Acute Physiology, and Chronic Health Evaluation (APACHE II) score, and survival and mortality rates were compared. In both groups after treatment, the levels of serum creatine kinase isozyme MB, creatine kinase, creatinine, glutamic-oxalacetic transaminease, and glutamate-pyruvate transaminase, and the APACHE II scores on the first, second, and seventh day decreased (P < 0.05), whereas the levels of serum acetylcholinesterase increased. The two groups showed no statistical differences in in-hospital duration, biochemical indicators, APACHE II score, hemodynamic parameters, survival rate, or the mortality rate (P > 0.05). In conclusion, SLED has similar hemodynamic stability to CHF and the two treatment methods have similar effects on ASOPP patients. More importantly, SLED plus HP is relatively economical and convenient for patients with ASOPP in clinical practice.