Background and aim: Laser is one of the most recent techniques which has widespread use in the treatment of many skin diseases. This technique has been successfully used to remove unwanted hairs in hirsutism. The aim of this study was to evaluate and compare the efficacy and safety of long-pulsed 755 nm alexandrite and long-pulsed 1064 nm Nd: YAG lasers individually and in combination for permanent hair removal. Materials and Methods: This single-blind randomized clinical trial was conducted on 25 patients. They were treated by alexandrite or Nd: YAG or combination of them in 4 sessions with 8 weeks intervals. The treatment was applied on their medial and lateral sides of both legs. All the parameters of the systems were set on the company defaults. Subjects were evaluated 1 and 8 months after completion of the treatment. Hair count was measured by Visiomed device and digital camera photographs every session. To calculate mean hair reduction, the difference between hair count before and after treatment was divided by hair count before treatment. Pain severity, measured by Visual Analogue Scale (VAS), and side effects (bullae, scar and pigmentation changes) were recorded every session. The data were analyzed with ANOVA, post hoc Tukey and chi square tests. Results: Fifteen patients completed the study and 10 patients were excluded due to appearance of bullae in 2 patients and refuse to continue in 8 patients. The mean hair reduction measured by Visiomed 8 months after last treatment was: 61.96 ±21.09, 60.03±23.40 and 68.05±21.23 percent for alexandrite, Nd: YAG and combination therapy, respectively. When digital camera photos were used for measurement of hair reduction these values were 85.99±11.62, 73.60±16.57 and 79.61±18.08 percent, respectively. The differences between the systems were not significant (ANOVA, P>0.05). In paired comparison of the systems, no significant differences were observed either (Tukey test). The incidence of adverse effects (hyperpigmentation) and pain severity were significantly greater in area received combination therapy (P=0.001).Conclusion: Both alexandrite and Nd:YAG laser systems were effective in hair removal. In contrast, combination therapy did not have more efficacy and also caused more side effects.