UNASSIGNED : Nigella sativa (N. sativa) seeds are used in the Iranian traditional medicine for the treatment of liver diseases. OBJECTIVE : To study the efficacy and safety of N. sativa seed oil in the treatment of patients with non-alcoholic fatty liver disease (NAFLD). METHODS : Sixty patients received 2.5 mL fully standardized N. sativa seed oil every 12 h and 60 other patients received placebo for 3 months. At the baseline and endpoint, hepatic steatosis ultrasound grade and blood levels of triglycerides, LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), ALT (alanine aminotransferase), AST (aspartate aminotransferase), blood urea nitrogen, creatinine and complete blood cell count as well as body mass index were determined in the oil and placebo groups and compared. RESULTS : Grade of hepatic steatosis was significantly reduced in the oil group compared to the placebo group (P = 0.004). Mean ± standard deviation of changes of variables in the oil and placebo groups were respectively 32.6 ± 16.6 and 14.2 ± 19.7% for ALT (P < 0/001), 29.4 ± 16.3 and 12.3 ± 16.8% for AST (P < 0.001), 10 ± 13.9 and 0.22 ± 18.2% for triglycerides (P = 0.001), 14.1 ± 9.8 and 9.2 ± 11.1% for LDL-C (P = 0.01), 9.5 ± 7.7 and 4.8 ± 6.5% for HDL-C (P = 0.001). However, the oil did not significantly affect the other outcome variables compared to the placebo (all P > 0.05). No adverse effect was observed. CONCLUSIONS : The N. sativa seed oil seems to be safe and improve liver steatosis and injury and blood levels of triglycerides, LDL-C and HDL-C in the NAFLD patients.