Background: Pregnancy striae, or stretch marks, are highly prevalent and often a source of cosmetic concern for many women, presenting challenges in both prevention and treatment. Objectives: This study aimed to evaluate the effect of vitamin D cream on pregnancy striae in the thigh area of first-time pregnant women. Methods: This triple-blind randomized clinical trial involved 60 primigravida women, aged 18 - 20 weeks, referred to Shahid Akbarabadi Hospital in Tehran, Iran, in 2022. Using blocked randomization, participants were assigned to two groups: The vitamin D cream intervention group (30 women) and the basic cream placebo group (30 women). Each cream was applied daily for 4 months, twice daily with a 12-hour interval. The severity of striae was assessed using the Atwal Scale before the intervention and at 4, 8, 12, and 16 weeks after the intervention commenced. Data analysis included descriptive statistics (frequency, minimum, maximum, mean, and standard deviation) and inferential statistics (chi-square, Fisher’s exact test, independent t-test, and Mann-Whitney test). Results: At the fourth, eighth, twelfth, and sixteenth weeks, the incidence of striae was as follows: Vitamin D group: 96.2%, 92.3%, 92.3%, and 88.5% without striae and 3.8%, 7.7%, 7.7%, and 11.5% with moderate erythema, respectively. Placebo group: 83.33%, 83.33%, 83.33%, and 66.67% without striae and 16.67%, 16.67%, 16.67%, and 33.33% with moderate erythema, respectively. No significant difference was found between the two groups regarding the severity of pregnancy striae at all follow-up times. Conclusions: Over the 4-month follow-up period, vitamin D cream did not demonstrate greater effectiveness than placebo in preventing or reducing the severity of pregnancy striae in the thigh area.