The high levels of musculoskeletal pain, in conjunction with the low levels of functional capacity, may negatively affect workers' health, efficiency, and productivity. This randomized controlled study investigated the efficacy of a 6-month comprehensive workplace exercise program on musculoskeletal pain and functional capacity in office workers. Seventy male and female office workers with musculoskeletal pain in any body area were randomly assigned to either an intervention (IG; n = 35) or a control group (CG; n = 35). The IG participated every working day (during working hours) in a 6-month supervised combined (flexibility, strength, and balance) exercise program (120 training sessions; five times/week) for the total body. The CG did not participate in any intervention. Musculoskeletal pains in nine body areas and functional capacity (flexibility, balance, and strength) of the lower and upper body were measured before and following the intervention. The IG significantly reduced duration and intensity of pain (43.1-70%; p = 0.000) as well as days of work absenteeism (84.6%; p = 0.000), while improving work capacity (87.1%; p = 0.000). Furthermore, the IG significantly increased cervical, handgrip, back, and leg maximal strength (10.3-27.1%; p = 0.000) and flexibility and balance (12.3-73.7%; p = 0.000). In CG, all musculoskeletal pain and functional capacity indices remained unchanged. In conclusion, this program may be effectively used to reduce musculoskeletal pain and improve functional capacity.