Background Heart valve replacement has many complications that affect patients and their family caregivers. Increasing patients' self-efficacy in dealing with complications and reducing the care burden of their caregivers are among the critical factors that impact their quality of life. Today, smartphone Apps allow access to reliable information without time and place restrictions. It also facilitates teaching and learning through low-cost and easily accessible methods. Objective This study was conducted to examine the effect of a smartphone App on the care burden of family caregivers and self-efficacy of patients undergoing heart valve surgery. Methodology A randomized clinical trial study with a pre-test / post-test design was conducted. Sixty patients undergoing mechanical heart valve surgery were referred to the Shahid Modarres Hospital and PT clinic in Tehran, and their family caregivers were randomly divided into intervention and control groups. The App was installed on the patients' smartphones for educational purposes, and they were given 8 weeks to use it. Sullivan's cardiac self-efficacy questionnaire and Novak and Guest's care burden questionnaire were completed for patients and their caregivers in both groups before and after the intervention, respectively. Data was statistically analyzed using descriptive and inferential statistics through SPSS-18 software. Findings There was no statistically significant difference between the two groups regarding demographic characteristics and the mean scores of self-efficacy and care burden before the intervention. However, after the intervention, the mean self-efficacy score increased to 47.43 +/- 5.43 in the intervention group and 32.23 +/- 3.25 in the control group, showing a significant improvement in patients' self-efficacy in the intervention group (P < 0.001). Although the mean self-efficacy score slightly increased in the control group, this increase was not statistically significant (P = 0.094). Furthermore, the mean score of care burden of caregivers after the intervention increased to 45.33 +/- 6.34 in the intervention group and 53.86 +/- 6.80 in the control group, showing a significant decrease in the care burden of caregivers in the intervention group compared to those in the control group (P < 0.001). Conclusion Based on the results, the designed smartphone App improved the self-efficacy of patients undergoing heart valve surgery while reducing the care burden of their family caregivers. Therefore, this App is recommended due to its effectiveness, ease of use, and low cost.