To evaluate the outcomes of patients with medium-sized hepatocellular carcinoma (HCC) who underwent percutaneous microwave ablation (MWA). We retrospectively reviewed all patients with a single medium-sized HCC who underwent percutaneous MWA from January 2010 to January 2013. Technical success, technical effectiveness and complications were subsequently observed. Survival curves were constructed using the Kaplan-Meier method. The Cox proportional hazards model was fitted to each variable. The relative prognostic significance of the variables for predicting overall survival rate, recurrence-free survival rate and local tumor recurrence(s) was assessed using univariate analysis. All variables with a P value < 0.20 were subjected to multivariate analysis. The study included 182 patients (mean age, 58 years; age range: 22-86 years) with a single HCC (mean size, 3.72 ± 0.54 cm; range: 3.02-5.00 cm). The estimated technical effectiveness rate was 93% in 182 patients. The major complication rate was 2.7% (5/182), including liver abscess in 4 cases, and abdominal bleeding at the puncture site in 1 case. Thirty-day mortality rate was 0.5% (1/182). One patient died due to liver abscess-related septicemia. Cumulative recurrence-free survival and overall survival (OS) rates were 51%, 36%, 27% and 89%, 74%, 60% at 1, 2, and 3 years, respectively. Age (P = 0.017) and tumor diameter (P = 0.029) were independent factors associated with local tumor recurrence. None of the factors had a statistically significant impact on recurrence-free survival. Serum albumin level (P = 0.009) and new lesion(s) (P = 0.029) were independently associated with OS. Percutaneous MWA is a relatively safe and effective treatment for patients with medium-sized HCC.