Background <p>Infertility is often considered a significant emotional challenge in a woman’s life, leading to heightened levels of psychological distress including stress, depression, and anxiety. Given the profound impact of these negative emotions, especially stress, on various aspects of life and fertility treatment outcomes, this study aimed to evaluate the effects of guided imagery relaxation on stress level among infertile women undergoing In vitro fertilization.</p> Methods <p>This randomized clinical trial was conducted on 60 infertile women preparing for In vitro fertilization in a private fertility clinic in Tehran. Subjects were randomly assigned to either the intervention (<i>n</i> = 30) or the control (<i>n</i> = 30) group. The intervention group engaged in six guided relaxation sessions, each lasting 45&#xa0;min, delivered twice a week via audio podcasts. The control group received routine care without additional interventions. Both groups completed the Newton Infertility Stress Questionnaire before and immediately after the intervention. Data were analyzed using SPSS version 16, employing both descriptive and inferential statistical methods.</p> Results <p>The average age of women in the intervention and control group were 35.21 ± 4.39 years and 34.93 ± 5.46 years, respectively. There was also no significant difference between the intervention and control groups in terms of age and other demographic and fertility variables (<i>P</i> &gt; 0.05). The total stress score before the intervention was 138.61 ± 28.40 in the intervention group and 138.00 ± 24.46 in the control group, and this difference was not statistically significant (<i>P</i> &gt; 0.05). The findings indicated a greater reduction in infertility-related stress scores and its subscales in the intervention group compared to the control group although this difference was not statistically significant (<i>P</i> &gt; 0.05). In addition, the overall stress score demonstrated a significant decrease in both the intervention (<i>P</i> = 0.03) and control (<i>P</i> = 0.002) groups after intervention.</p> Conclusion <p>Considering the observed reduction in stress among infertile women following guided imagery relaxation, this technique may serve as a beneficial complementary approach in infertility treatment. Integrating relaxation methods alongside medical treatments and psychological counseling could potentially reduce stress, enhance well-being, and improve treatment outcomes.</p> Trial registration <p>This clinical trial registered with the Clinical Trials Registry of Iran under the registration number IRCT20160821029446N9 at 2021-09-03.</p>