The effects of community-wide interventions to reduce resistance rates are poorly understood. This study evaluated the effect of reduced antimicrobial usage on the spread of penicillin-nonsusceptible pneumococci (PNSP) in four communities in Iceland. The study was performed after interventions to reduce antimicrobial usage and compared to an identical study performed 5 years before. A randomized sample of 953 children was chosen from all 2,900 1- to 6-year-old children living in four well-defined communities. The main outcome measures were nasopharyngeal carriage of PNSP and individual and community use of antimicrobials. Pneumococci were carried by 51.7% of the 743 children enrolled, and 8.1% of the pneumococci were PNSP as opposed to 8.5% in the previous study. The antimicrobial use of participants had been reduced from 1.5 to 1.1 courses/year and the overall use among children <7 years old living in the study areas from 13.6 to 11.1 defined daily dosages/1000 children per day. The prevalence of PNSP increased in the two areas furthest away from the capital area despite reduced consumption. The major risk factors for carriage of PNSP remained the same. Interventions can be effective in reducing antimicrobial use. Pandemic multiresistant clones can also spread fast in small communities with low antimicrobial use, where their appearance may be delayed compared to highly populated urban areas. Clonal spread and herd immunity are important factors to be considered in the evaluation of intervention effects.