Background: PCV7 was introduced as universal childhood vaccination in Israel in July 2009 and PCV13 in November 2010. Here we report data on adult invasive pneumococcal disease (IPD), two years post PCV7 implementation and before an expected effect of PCV13. Methods: An ongoing nationwide active-surveillance (all 27 laboratories performing blood cultures in Israel), providing all blood & CSF S. pneumoniae isolates from persons >18 y was initiated in July 2009. Capture-recapture method assured reporting of >95% cases. All isolates were serotyped in one central laboratory. IPD outcome and medical history were recorded in 90%. Second year post PCV implementation is compared to the first year. Results: During July 2009 to June 2011, 970 IPD cases were reported (annual incidence [/100,000] of 9.17 and 10.16 in the two consecutive years, respectively). Respective case fatality rates (CFRs) were 20% and 19.1%. Incidence of IPD and CFR increased with age and number of comorbidities. Incidence rate was significantly greater during the second winter, 7.79/100,000 vs. 6.14/100,000 in first winter, p = 0.004, with a non-significant decrease during summer months (3.02 to 2.48/100,000). The proportion of IPD cases due to PCV7-serotypes decreased from 27.5% to 13.1% (first to second year) (p<0.001). Yet, non-PCV13-strains increased from 32.7% to 40.2% (p = 0.017). The increase in non-PCV13-strains was highly significant in immunocompromised patients and to a lesser degree in non-immunocompromised at risk or in older patients (>64 y). Among younger/healthier patients serotype 5 was the major increasing serotype. Penicillin and ceftriaxone resistance decreased significantly in the second year. Conclusions: While overall annual incidence of IPD did not change, the indirect effect of PCV7 vaccination was evident by the significant decrease in PCV7 serotypes across all age groups. Increase in non-VT13 strains was significant in immunocompromised patients. A longer follow-up is required to appreciate the full effect of infant vaccination on annual IPD.