Purpose: To examine the influence of isometric handgrip exercise (ISO EX) on pain perception and blood pressure in men and women, Methods: Fifteen men and 16 women completed max and submax ISO EX consisting of squeezing a hand dynamometer with the right hand as hard as possible for the max session, and squeezing between 40% and 50% of max for 2 min for the submax session. Pain thresholds (PT), pain ratings (PR), blued pressure (SBP and DBP), and heart rate (HR) were assessed while a noxious pressure stimulus was applied to the right forefinger for 2 min before and after ISO EX. Dais were analyzed with a 2 (gender) x 2 (trials) ANOVA. Results: Results indicated a significant trials effect and a significant gender by trials interaction (P < 0.05) for PT for the max and submax sessions. Women had lower PT before ISO EX in comparison with the men. In addition, PT for the women increased significantly after ISO EX but did not change for the men. There were significant gender and trials effects (P < 0.05) for SEP for the submax session. Women had lower SEP before ISO EX, and SEP increased after ISO EX. DBP was also found to be lower (P < 0.05) in women before max and submax ISO EX, with DBP increasing after submax ISO EX in men and women. PR were found to be lower after max ISO EX in men and women, whereas PR were found to be lower in women after submax ISO EX. Conclusion: It is concluded that: 1) men and women differed in PT, SEP, and DBP before ISO EX; and 2) analgesia after ISO EX is observed more consistently in women.