Background and ObjectivesTo compare the efficacy of the long‐pulsed Nd:YAG (1,064 nm) laser versus the Q‐Switched Nd:YAG (1,064 nm) laser in treatment of onychomycosis.Study Design/Materials and MethodsThis is a prospective cohort study. It was carried out on 20 patients with clinical and mycological evidence of onychomycosis who were randomly assigned into two groups; group I: included 10 patients treated with biweekly sessions of long‐pulsed Nd:YAG (1064 nm) laser and group II; included 10 patients treated with monthly sessions of Q‐Switched Nd:YAG (1064 nm) laser. The assessment was done using proximal nail measurement and microscopic examination using 10–20% potassium hydroxide solution and culture on Sabouraud's dextrose agar. All patients were followed up for 6 months after the last treatment session.ResultsFungal isolates in the present study were grouped into yeast in 50%, non‐dermatophyte moulds in 10%, while dermatophyte infection was detected in 40%. Each group showed a statistically significant improvement in proximal nail plate measurements with no statistically significant difference between both groups. Mycological cure was only achieved in 40% of group I and 30% of group II. Patient satisfaction was higher in group II.ConclusionsBoth long‐pulsed Nd:YAG (1064 nm) and Q‐Switched Nd:YAG (1064 nm) laser systems can be used as a safe and effective modality in the treatment of onychomycosis, particularly in patients who refuse or have a contraindication to oral antifungal treatment. Lasers Surg. Med. 00:00–00, 2019. © 2019 Wiley Periodicals, Inc.