Background: Free muscle flaps can develop significant postoperative edema and wound exudation, thereby increasing interstitial pressure and potentially compromising microcirculation. While concerns exist regarding negative pressure wound therapy (NPWT) to compress free flaps and hinder monitoring, recent studies have indicated a reduction in edema and an increase in blood flow. Objective: To compare microcirculation in free latissimus dorsi muscle (LDM) flaps dressed with and without NPWT. Methods: This retrospective cohort study analyzed prospectively collected data of patients who received free LDM flap reconstruction. Patients were separated into two groups according to management with or without NPWT. Microcirculation was evaluated continuously for up to 72 h utilizing laser doppler flowmetry and tissue spectrometry. Results: In total, n = 61 patients (26 females, 35 males) with an average age of 56.90 (17.4) years were included. NPWT was applied in 12 patients, while a regular cotton dressing was used in 49 patients. Overall, no significant differences in the number of minor and major complications were observed between groups. Both groups showed an increase in microvascular flow over the investigated time period. The flow showed higher absolute values in the NPWT group, reaching statistical significance at 12 h post-anastomosis, p = 0.038. There was a tendency for lower rHb values in the NPWT group, without reaching statistical significance. Conclusions: The presented study confirms the increase in microvascular flow after NPWT application. Whilst ensuring continuous free flap monitoring utilizing laser doppler flowmetry and spectrometry, the data further support the safety of NPWT application without risking vascular compromise due to external compression.