Background: Pneumococcal disease is a major cause of morbidity and death, especially among elders and other people at high risk. In spite of long-standing national recommendations for its use, pneumococcal vaccine is underused, with 70% or more of targeted persons as yet unimmunized. Concern about side effects is a barrier to successful vaccine delivery. Methods: Persons attending a walk-in pneumococcal vaccination clinic were surveyed by use of structured telephone interviews. They were asked about health characteristics and local and systemic symptoms experienced during the week after their vaccination (postvaccination period). These responses were compared with the symptoms they reported for the 7 days immediately preceding their interview (the comparison period). Results: A total of 1006 persons were interviewed a mean of 65.4 days after their vaccination. They had an average age of 69.9 years, and approximately 95% were in a high-risk group targeted for pneumococcal vaccination. For all systemic symptoms including fever, rash, myalgias, fatigue, malaise, and headache, subjects reported similar or lower rates during the postvaccination week than during the comparison week. Local reactions occurred in 28.2% of subjects. These local symptoms were mild to moderate for more than 90% of subjects and rarely resulted in the need to decrease the use of their arm. Conclusion: Pneumococcal vaccination was not associated with an increase in systemic symptoms but was associated with mild to moderate local symptoms in about one fourth of vaccine recipients. These findings should help health care providers and their patients address an important barrier to pneumococcal immunization.