<b><i>Objective:</i></b> Often a sick or an anxious person can experience pain or anxiety relief if another person holds his or her hand. In this study, we conducted investigations to determine whether hand-holding during cystoscopy decreases patient anxiety, pain, and dissatisfaction while at the same time increasing patient comfort and tolerance during the procedure. <b><i>Patients and Methods:</i></b> Eighty-six male patients who underwent flexible cystoscopy between November 2015 and March 2017 were randomized as follows: hand-holding (group I, <i>n</i> = 43) or non-hand-holding (group II, <i>n</i> = 43) during the procedure. Before flexible cystoscopy, lidocaine gel was instilled in the urethra. Patients’ anxiety levels were quantified using the State-Trait Anxiety Inventory. A visual analog scale (0–10) was used for self-assessment of satisfaction, discomfort, and willingness to undergo repeat cystoscopy. <b><i>Results:</i></b> Demographic characteristics, mean age, procedure duration, procedure indications, and preprocedural analyses did not differ significantly between the 2 groups. In group I, the postprocedural mean anxiety level, pain score, heart rate, and systolic blood pressure were significantly lower compared with those in group II (<i>p</i> = 0.009, <i>p</i> = 0.003, <i>p</i> = 0.022, and <i>p</i> = 0.014, respectively). In group I, postprocedural mean satisfaction score were higher, and patients were more likely to undergo a repeat cystoscopy, compared with those in group II (<i>p</i> = 0.001 and <i>p</i> = 0.004, respectively). <b><i>Conclusions:</i></b> Hand-holding during cystoscopy significantly reduced patients’ feelings of anxiety, pain, discomfort, and dissatisfaction. Hand-holding served as a simple, inexpensive, and effective adjunct to sedation during cystoscopy.