Aim. This study aimed to evaluate the peri-implant soft tissue response to customized healing abutments (CHAs) made of titanium and polyetheretherketone (PEEK). Methods. Titanium and PEEK CHAs were mounted on bone-level dental implants in bilateral edentulous patients in a randomized split-mouth study design. After a three-week healing period, the clinical parameters of the peri-implant soft tissues were assessed. The value of marginal bone resorption was measured by cone-beam computed tomography. In addition, peri-implant crevicular fluid samples were obtained to identify periodontal pathogenic bacteria, cytokine levels, and active neutrophil collagenase (aMMP-8) concentration. Microcirculation and oxygenation parameters were assessed using laser Doppler flowmetry and optical tissue oximetry. In addition, wavelet analysis was conducted to study blood flow control mechanisms. Results. Out of the 23 participants initially recruited, 20 were assessed after titanium and PEEK CHA installation due to losses to follow-up. The peri-implant soft tissue around 27 titanium and 25 PEEK CHAs was evaluated during follow-ups. No differences were found in the values of marginal bone resorption, cytokine levels, or total bacterial load (p>0.05). PEEK CHAs demonstrated lower bleeding on probing values, less plaque accumulation, and faster relief of ischemia and hypoxia. Although aMMP-8 concentration was higher in the PEEK group, the values were within normal limits. Conclusions. The results of this comparative study showed a positive soft tissue response to PEEK CHAs. However, further studies comparing the effectiveness of different materials for CHAs should be carried out, considering their specific physical properties and processing protocols.