BackgroundPrimary axillary hyperhidrosis (PAH) affects 1−5% of the world's population who has an unmet need for improved treatments. The heating of sweat glands with specific microwave therapy has shown promising results, yet, treatment with widely available devices such as long‐pulsed Neodymium Yttrium Aluminum Garnet (Nd:YAG) lasers, diode lasers or Intense Pulsed Light (IPL) may serve as pragmatic alternatives.ObjectivesTo compare sweat secretion of treated versus untreated contralateral control axilla 1−3 months after one session of Nd:YAG laser or IPL in patients with PAH.MethodsA within‐person randomized controlled trial. Patients were randomized to receive either one session of Nd:YAG laser or IPL in one axilla with the contra‐lateral serving as control. Sweat production was assessed by gravimetry, trans‐epidermal water loss, hyperhidrosis disease severity scale and dynamic optical coherence tomography. Mixed‐effects models were used to handle the within‐person design, containing both fixed effect factors (side, group, and subgroup), and random effects (patients), while also adjusting for the level at baseline.ResultsA total of 20 patients were enrolled. At follow‐up 1−3 months after treatment, sweat secretion was not affected in the treated axilla when compared to the control axillae (0.01 [95%CI: −0.04 to 0.05]; p = 0.68). In the Nd:YAG subgroup (10 patients), least squares means for sweat secretion was 0.18 mg/5 min in the treated versus 0.15 mg/5 min in the control axilla, respectively, corresponding to a statistically insignificant mean difference of 0.02 mg/5 min (95% CI: −0.06 to 0.11; p = 0.54). In the IPL subgroup (10 patients), sweat secretion was 0.06 mg/5 min in the treated axilla versus 0.07 mg/5 min in the control axilla with a statistically insignificant difference of –0.01 points (95% CI: −0.03 to 0.02; p = 0.46). Likewise, none of the secondary outcomes were significantly affected by treatment. However, both treatments appeared safe and well tolerated with no adverse effects reported at follow‐up.ConclusionsOne treatment with external 1064 nm Nd:YAG laser or 640 nm IPL at commercially available settings, failed to demonstrate clinical benefit in treating PAH, with narrow confidence intervals implying that this was not due to a type‐2 error.